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Sample records for acetaminophen-induced acute hepatic

  1. Role of Protective Effect of L-Carnitine against Acute Acetaminophen Induced Hepatic Toxicity in Adult Albino Rats

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    Zeinab M. Gebaly* and Gamal M. Aboul Hassan

    2012-10-01

    Full Text Available Background: Acetaminophen, a widely used analgesic and antipyretic is known to cause hepatic injury in humans and experimental animals when administered in high doses. It was reported that toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing to the beta-oxidation of fatty acid in the mitochondria. It is a known antioxidant with protective effects against lipid peroxidation. This study aimed to investigate the possible beneficial effect of L-carnitine as an antioxidant agent against acetaminophen induced hepatic toxicity in rats. Material and Methods: Four rat groups (N=7 in each group. Group I is the control, group II received 500 mg/kg/ body weight of L-carnitine for 7 days by oral route, group III received 640/kg/ bw of acetaminophen by oral route, group IV acute acetaminophen group pretreated with L-carnitine for 7 days by gastric tube gavage tube. The liver of all rats were removed for investigation using light and electro microscopic studies. Results: Acetaminophen caused massive centrilobular necrosis and massive degenerative changes. The electron-microscopic study showed few mitochondria, increased fat droplets and scanty smooth endoplasmic reticulum (SER, rough endoplasmic reticulum (RER.These changes were reduced by L-carnitine pretreatment. Conclusion: those results suggest that acetaminophen results damage in the liver as an acute effect and L-carnitine ameliorated the adverse effects of acetaminophen via its antioxidant role

  2. Effect of sesame oil against acetaminophen-induced acute oxidative hepatic damage in rats.

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    Chandrasekaran, Victor Raj Mohan; Wan, Chang-Hsin; Liu, Li-Lian; Hsu, Dur-Zong; Liu, Ming-Yie

    2008-08-01

    Acetaminophen (APAP) overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of sesame oil on APAP-induced acute liver injury. Male Wistar rats were given APAP (1,000 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased aspartate transaminase, alanine transaminase, lipid peroxidation, and superoxide anion and hydroxyl radical generation levels; it also induced glutathione depletion. Sesame oil (8 mL/kg; orally) did not alter the gastric absorption of APAP, but it inhibited all the parameters altered by APAP and protected the rats against APAP-induced acute liver injury. We hypothesize that sesame oil maintained the intracellular glutathione levels, reduced reactive oxygen species levels, and inhibited lipid peroxidation in rats with APAP-induced acute liver injury.

  3. Acetaminophen-induced acute liver injury in HCV transgenic mice

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

    2013-01-15

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

  4. Effects of sesame oil against after the onset of acetaminophen-induced acute hepatic injury in rats.

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    Chandrasekaran, Victor Raj Mohan; Chien, Se-Ping; Hsu, Dur-Zong; Chang, Yu-Chung; Liu, Ming-Yie

    2010-01-01

    Acetaminophen (APAP) is a safe and effective analgesic and antipyretic when used at therapeutic levels. However, an acute or cumulative overdose can cause severe liver injury with the potential to progress to liver failure in humans and experimental animals. Much attention has been paid to the development of an antioxidant that protects against APAP-induced acute hepatic injury. Hence, we aimed to investigate the effect of sesame oil against after the onset of acute hepatic injury in APAP-overdosed rats. Male Wistar rats were first given 2 oral doses (1,000 mg/kg each) of APAP (at 0 and 24 hours) and then 1 oral dose of sesame oil (8 mL/kg at 24 hours). After 48 hours, APAP increased aspartate and alanine aminotransferase levels in the rats' serum and centrilobular necrosis in liver tissue. In addition, APAP significantly decreased the rats' glutathione levels and mitochondrial aconitase activity, but increased superoxide anion, hydroxyl radical, and lipid peroxidation levels. Oral sesame oil (8 mL/kg, given at 24 hours) reversed all APAP-altered parameters and protected the rats against APAP-induced acute liver injury. We hypothesize that sesame oil acts as a useful agent that maintains intracellular glutathione levels and inhibits reactive oxygen species, thereby protecting rats against after the onset of APAP-induced acute oxidative liver injury.

  5. Croton zehntneri Essential oil prevents acetaminophen-induced acute hepatotoxicity in mice

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    Maria Goretti R. Queiroz

    2008-10-01

    Full Text Available Hepatoprotective activity of Croton zehntneri Pax & Hoffman (Euphorbiaceae leaf essential oil (EOCz was evaluated against single dose of acetaminophen-induced (500 mg/kg, p.o. acute hepatotoxicity in mice. EOCz significantly protected the hepatotoxicity as evident from the activities of serum glutamate pyruvate transaminase (GPT, serum glutamate oxaloacetate transaminase (GOT activities, that were significantly (p<0.01 elevated in the acetaminophen alone treated animals. Histopathological examinations of liver tissue corroborated well with the biochemical changes. Hepatic steatosis, hydropic degeneration and necrosis were observed in the acetaminophen treated group, while these were completely absent in the standard and EOCz treated groups. In conclusion, these data suggest that the Croton zehntneri essential oil can prevent hepatic injuries from acetaminophen-induced hepatotoxicity in mice.

  6. Acetaminophen-Induced Acute Pancreatitis. A Case Report

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    Hisato Igarashi

    2009-09-01

    Full Text Available Context Drug-induced acute pancreatitis is rare but should not be overlooked in a patient who presents with idiopathic acute pancreatitis. More than 100 drugs have been implicated in causing the disease: acetaminophen has been associated with acute pancreatitis in cases where there has been an overdose of drugs; however, the frequency is rare. Case report We report the case of a 35-year-old woman who presented with acute pancreatitis and severe metabolic acidosis after overdosing on a drug containing acetaminophen. She improved dramatically after intensive care; however, she showed recurrent episodes after re-overdosing on the same drug. With her self re-challenge test, she was diagnosed as having acetaminophen-induced pancreatitis and metabolic acidosis. A review of the relevant literature is also presented. Conclusions Drug-induced acute pancreatitis is often challenging for clinicians and a detailed mechanism is unknown. It is very important to rule out drug-induced pancreatitis when treating pancreatitis with an unknown etiology.

  7. Protective effect of rosiglitazone against acetaminophen-induced acute liver injury is associated with down-regulation of hepatic NADPH oxidases.

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    Wang, Jun-Xian; Zhang, Cheng; Fu, Lin; Zhang, Da-Gang; Wang, Bi-Wei; Zhang, Zhi-Hui; Chen, Yuan-Hua; Lu, Yan; Chen, Xi; Xu, De-Xiang

    2017-01-04

    The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. The aim of the present study was to investigate the effects of rosiglitazone (RSG), a synthetic PPAR-γ agonist, on acetaminophen (APAP)-induced acute liver injury. Male CD-1 mice were injected with APAP (300mg/kg). Some mice were pretreated with RSG (20mg/kg) 48, 24 and 1h before APAP injection. As expected, RSG pretreatment alleviated APAP-induced acute liver injury. Moreover, RSG pretreatment attenuated APAP-induced hepatic cell death and improved the survival. Although it did not affect hepatic cytochrome P450 (CYP)2E1 expression, RSG pretreatment attenuated reduction of hepatic glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd) and glutathione S-transferase (GST) activities, inhibited upregulation of hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-2 and NOX-4, and alleviated hepatic GSH depletion during APAP-induced acute liver injury. In addition, RSG pretreatment suppressed activation of hepatic nuclear factor kappa B (NF-κB) and extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling during APAP-induced acute liver injury. These results provide a novel mechanistic explanation for RSG-mediated protection against APAP-induced acute liver injury. The present results suggest that synthetic PPAR-γ agonists might be effective agents for preventing the progression of APAP-induced acute liver injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Treatment of acetaminophen-induced hepatitis and fulminant hepatic failure with extracorporeal sorbent-based devices.

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    Ash, Stephen R; Caldwell, Cary A; Singer, Greg G; Lowell, Jeff A; Howard, Todd K; Rustgi, Vinod K

    2002-01-01

    When a patient with acetaminophen overdose arrives in the emergency room more than 14 hours after ingestion, the value of N-acetylcysteine is unproven and patient mortality is at least 10%. Anecdotal case reports have indicated benefit of extracorporeal detoxification of these late-arriving patients with acetaminophen overdose. We identified 10 patients with serious acetaminophen overdose, 8 that arrived in the emergency room 16 to 44 hours after acetaminophen overdose with plasma levels predicting severe hepatic toxicity, and 2 that arrived in the emergency room 8 to 12 hours after overdose but with exceedingly high levels. All patients developed severe hepatitis (mean peak alanine aminotransferase, 4,052; mean peak protime, 25 seconds). At 16 to 68 hours after overdose, the patients were treated for 4 to 6 hours with the Liver Dialysis System (Hemocleanse Inc, W. Lafayette, IN), a single-access hemodiabsorption system indicated for treatment of serious drug overdose and for treatment of hepatic encephalopathy. Acetaminophen levels fell an average of 73% during treatment. Treatment was repeated 24 or 48 hours later if acetaminophen was still measurable in plasma. All 10 patients recovered intrinsic liver function and general health, with liver enzymes starting to normalize 24 hours after treatment, and were discharged 3 to 7 days after overdose. No patient required liver transplant. Because market introduction of Liver Dialysis, there have been 40 more patients with acetaminophen-induced hepatotoxicity treated with Liver Dialysis. All have recovered liver function without long-term sequelae. Though most of these patients with already established hepatic toxicity from acetaminophen would recover without extracorporeal blood therapy, treatment with the Liver Dialysis System should assure recovery from acute hepatic failure, and may shorten the clinical course of the illness.

  9. Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

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    Yu Ri Kim

    2013-01-01

    Full Text Available High doses of acetaminophen (APAP; N-acetyl-p-aminophenol cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg. Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity.

  10. Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples

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    Robim M. Rodrigues

    2016-06-01

    Full Text Available This data set is composed of transcriptomics analyses of (i liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF and (ii hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC. Data from primary human hepatocytes was also added to the data set “Open TG-GATEs: a large-scale toxicogenomics database” (Igarashi et al., 2015 [1]. Changes in gene expression due to acetaminophen intoxication as well as comparative information between human in vivo and in vitro samples are provided. The microarray data have been deposited in NCBI׳s Gene Expression Omnibus and are accessible through GEO Series accession number GEO: GSE74000. The provided data is used to evaluate the predictive capacity of each hepatic in vitro system and can be directly compared with large-scale publically available toxicogenomics databases. Further interpretation and discussion of these data feature in the corresponding research article “Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems” (Rodrigues et al., 2016 [2].

  11. Croton zehntneri Essential oil prevents acetaminophen-induced acute hepatotoxicity in mice

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    Maria Goretti R. Queiroz; José Henrique L. Cardoso; Tomé, Adriana R; Roberto C. P. Lima Jr.; Jamile M. Ferreira; Daniel F. Sousa; Felipe C. Lima; Campos, Adriana R.

    2008-01-01

    Hepatoprotective activity of Croton zehntneri Pax & Hoffman (Euphorbiaceae) leaf essential oil (EOCz) was evaluated against single dose of acetaminophen-induced (500 mg/kg, p.o.) acute hepatotoxicity in mice. EOCz significantly protected the hepatotoxicity as evident from the activities of serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT) activities, that were significantly (p

  12. The protective role of Gongronema latifolium in acetaminophen induced hepatic toxicity in Wistar rats

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    Nnodim Johnkennedy; Emejulu Adamma

    2011-01-01

    Objective: To evaluate the protective effect of leaf extract of Gongronema latifolium (G. latifolium) against acute acetaminophen induced hepatic toxicity in Wistar rats. Methods:Thirty six Wistar rats were divided into 6 groups with 6 rats in each group. Animals in group 1 and 2 were administered with 600 mg/kg b.w. of acetaminophen only and acetaminophen plus 100 mg/kg b.w. of caffeine by oral gavages, respectively. Experimental groups 3 and 4 were treated as in group 1 but in addition received 200 and 400 mg/kg b.w., respectively of the leaf extract of G. latifolium by oral gavages. The experimental groups 5 and 6 were treated as in group 2 and in addition received 200 and 400 mg/kg b.w. of leaf extract of G. latifolium, respectively. The treatment lasted for 14 days. Results: The results obtained showed that the serum glutamic-oxalacetic transaminease (AST), glutamic-pyruvic transaminase (ALT) and alkaline phosphatase (ALP) levels had a greater increase in group 2 than in group 1 but dropped marginally in groups 3 and 4. However, in groups 5 and 6, AST, ALT and ALP were significantly reduced (P<0.05). Similarly, serum protein levels were significantly increased in groups 3, 4, 5 and 6 when compared with group 1 and 2. Conclusions: It can be concluded that extract of G. latifolium offers protection against acetaminophen and caffeinated acetaminophen toxicity in Wistar rats.

  13. Acetaminophen-induced acute liver injury in mice.

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    Mossanen, J C; Tacke, F

    2015-04-01

    The induction of acute hepatic damage by acetaminophen (N-acetyl-p-aminophenol [APAP]), also termed paracetamol, is one of the most commonly used experimental models of acute liver injury in mice. The specific values of this model are the highly reproducible, dose-dependent hepatotoxicity of APAP and its outstanding translational importance, because acetaminophen overdose is one of the most frequent reasons for acute liver failure (ALF) in humans. However, preparation of concentrated APAP working solutions, application routes, fasting period and variability due to sex, genetic background or barrier environment represent important considerations to be taken into account before implementing this model. This standard operating procedure (SOP) provides a detailed protocol for APAP preparation and application in mice, aimed at facilitating comparability between research groups as well as minimizing animal numbers and distress. The mouse model of acetaminophen poisoning therefore helps to unravel the pathogenesis of APAP-induced toxicity or subsequent immune responses in order to explore new therapeutic interventions for improving the prognosis of ALF in patients.

  14. Gastric emptying in rats with acetaminophen-induced hepatitis

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    Hessel G.

    1998-01-01

    Full Text Available The objective of this work was to study the gastric emptying (GE of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each. Group I was fed a sucrose diet throughout the experiment (66 h while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each. Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg. Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 µg/ml than in group IB (87 µg/ml. The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values. The correlation between gastric retention and AST levels was significant (P<0.05 for group IIB for the three test meals: r = 0.73, 0.67 and 0.68 for saline, glucose and mayonnaise, respectively. We conclude that GE is altered in rats with hepatic lesions induced by acetaminophen, and that these alterations may be related to the liver cell necrosis caused by the drug.

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

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

    2013-01-01

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

  16. NADH:ubiquinone reductase and succinate dehydrogenase activity in the liver of rats with acetaminophen-induced toxic hepatitis on the background of alimentary protein deficiency

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    G. P. Kopylchuk

    2015-02-01

    Full Text Available The ratio between the redox forms of the nicotinamide coenzymes and key enzymatic activity of the I and II respiratory chain complexes in the liver cells mitochondria of rats with acetaminophen-induced hepatitis under the conditions of alimentary deprivation of protein was studied. It was estimated, that under the conditions of acute acetaminophen-induced hepatitis of rats kept on a low-protein diet during 4 weeks a significant decrease of the NADH:ubiquinone reductase and succinate dehydrogenase activity with simultaneous increase of the ratio between redox forms of the nicotinamide coenzymes (NAD+/NADН is observed compared to the same indices in the liver cells of animals with experimental hepatitis kept on the ration balanced by all nutrients. Results of research may become basic ones for the biochemical rationale for the approaches directed to the correction and elimination of the consequences­ of energy exchange in the toxic hepatitis, induced on the background of protein deficiency.

  17. Aloe vera attenuated liver injury in mice with acetaminophen-induced hepatitis.

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    Werawatganon, Duangporn; Linlawan, Sittikorn; Thanapirom, Kessarin; Somanawat, Kanjana; Klaikeaw, Naruemon; Rerknimitr, Rungsun; Siriviriyakul, Prasong

    2014-07-08

    An overdose of the acetaminophen causes liver injury. This study aims to examine the anti-oxidative, anti-inflammatory effects of Aloe vera in mice with acetaminophen induced hepatitis. Male mice were randomly divided into three groups (n = 8 each). Control group were given orally distilled water (DW). APAP group were given orally N-acetyl-P-aminophenol (APAP) 400 mg/kg suspended in DW. Aloe vera-treated group were given orally APAP and Aloe vera (150 mg/kg) suspended in DW. Twenty-four hours later, the liver was removed to determine hepatic malondialdehyde (MDA), hepatic glutathione (GSH), the number of interleukin (IL)-12 and IL-18 positive stained cells (%) by immunohistochemistry method, and histopathological examination. Then, the serum was collected to determine transaminase (ALT). In APAP group, ALT, hepatic MDA and the number of IL-12 and IL-18 positive stained cells were significantly increased when compared to control group (1210.50 ± 533.86 vs 85.28 ± 28.27 U/L, 3.60 ± 1.50 vs 1.38 ± 0.15 nmol/mg protein, 12.18 ± 1.10 vs 1.84 ± 1.29%, and 13.26 ± 0.90 vs 2.54 ± 1.29%, P = 0.000, respectively), whereas hepatic GSH was significantly decreased when compared to control group (5.98 ± 0.30 vs 11.65 ± 0.43 nmol/mg protein, P = 0.000). The mean level of ALT, hepatic MDA, the number of IL-12 and IL-18 positive stained cells, and hepatic GSH in Aloe vera-treated group were improved as compared with APAP group (606.38 ± 495.45 vs 1210.50 ± 533.86 U/L, P = 0.024; 1.49 ± 0.64 vs 3.60 ± 1.50 nmol/mg protein, P = 0.001; 5.56 ± 1.25 vs 12.18 ± 1.10%, P = 0.000; 6.23 ± 0.94 vs 13.26 ± 0.90%, P = 0.000; and 10.02 ± 0.20 vs 5.98 ± 0.30 nmol/mg protein, P = 0.000, respectively). Moreover, in the APAP group, the liver showed extensive hemorrhagic hepatic necrosis at all zones while in Aloe vera-treated group, the liver architecture was improved histopathology. APAP overdose can cause liver injury. Our result indicate that Aloe vera attenuate APAP

  18. A case of acetaminophen-induced acute tubulointerstitial nephritis in adult.

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    Inoue, Dan; Usui, Ryosuke; Nitta, Kosaku; Koike, Minako

    2017-08-11

    We report a case of allergic acute tubulointerstitial nephritis (TIN) induced by acetaminophen in a 48-year-old Japanese man with no past medical history. Two days after receiving the non-steroidal anti-inflammatory drug (NSAID) loxoprofen for left shoulder pain, he developed cold symptoms such as fever and sore throat. He then took a 300 mg dose of acetaminophen three times a day and a 100 mg dose of minocycline hydrochloride twice a day for 7 days. Because there was no improvement in his symptoms, he consulted a local clinic again, where blood tests revealed renal insufficiency, and he was, then, referred to our hospital for evaluation of kidney function. Renal biopsy revealed acute TIN, and Ga-67 scintigraphy showed diffuse uptake in bilateral kidneys. A drug-induced lymphocyte stimulation test (DLST) was positive for acetaminophen and negative for loxoprofen and minocycline. Based on these findings, we made a diagnosis of acetaminophen-induced TIN. We treated the patient with three courses of semi-pulse steroid therapy, after which his fever went down, and his serum creatinine level recovered from 2.09 to 1.43 mg/dL. Although we medical doctors think that therapeutic dose of acetaminophen retains high safety, it is important to keep in mind that acetaminophen can cause allergic acute TIN.

  19. 8-甲氧补骨脂素对对乙酰氨基酚致小鼠急性肝损伤的保护作用%Protective Effect of 8-Methoxypsoralen against Acetaminophen-induced Acute Hepatic Injury in Mice

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    魏鹏; 刘伟霞; 贾凤兰; 阮明; 张宝旭

    2012-01-01

    OBJECTIVE To investigate the hepatoprotective effect of 8-methoxypsoralen against acetaminophen-induced acute hepatic injury in mice. METHODS Liver injury model of mice was induced by subcutaneous injection of acetaminophen. Twenty-four hours later, the activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST) and lactate dehydroge- nase (LDH) were determined, and the liver tissues weTe collected for histopathological assessment by HE staining under light microscope. The ratio of glutathione(GSH) and oxidized glutathione(GSSG), and the content of GSH, GSSG and malondialdehyde (MDA) in liver homogenate were also measured. RESULTS Compared with the normal control group, the model group could markedly increase serum ALT, AST and LDH activities, and the degeneration and necrosis could be observed in liver tissues. Compared with die model group, 8-methoxypsoralen could markedly decrease serum ,ALT, AST and LDH activities, reduce the MDA level in liver homogenate, and increase GSH content and the ratio of GSH/GSSG in the liver homogenate The hepatic histopathological changes in liver were also significantly ameliorated. CONCLUSION The 8-methoxypsoralen can prevent the liver from acetaminophen-induced acute hepatic injury.%目的 研究8-甲氧补骨脂素(8-methoxypsoralen,8-MOP)对对乙酰氨基酚(acetaminophen,APAP)致小鼠急性肝损伤的保护作用.方法 采用对乙酰氨基酚所致小鼠急性肝损伤模型.24 h后,检测小鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH);留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化;制备肝匀浆,测定肝中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)和丙二醛(MDA)的含量.结果 与正常对照组比较,模型组小鼠血清中ALT、AST和LDH活性明显升高,肝脏组织出现明显的肝细胞变性坏死;与模型组相比,8-甲氧补骨脂素可以明显降低小鼠血清

  20. Role of N-acetylcysteine treatment in non-acetaminophen-induced acute liver failure: A prospective study

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    Nabi, Tauseef; Nabi, Sumaiya; Rafiq, Nadeema; Shah, Altaf

    2017-01-01

    Background/Aims: Acute liver failure (ALF) is a rare but severe medical emergency. To date, there is no established treatment for non-acetaminophen-induced acute liver failure (NAI-ALF) other than liver transplantation, and little is known about the use of N-acetylcysteine (NAC) in NAI-ALF. A randomized case control study was conducted with the aim to determine the effect of NAC on the mortality of NAI-ALF patients, as well as to evaluate the safety and efficacy of NAC use. Patients and Methods: A total of 80 patients diagnosed with NAI-ALF were included in the study. Forty patients received NAC infusion for 72 h whereas the control group received placebo. The variables evaluated were demographic characteristics, signs and symptoms, biochemical parameters, and clinical course during hospitalization. Results: The two groups (NAC and control) were comparable for various baseline characteristics (such as etiology of ALF, INR, alanine aminotransferase, creatinine, albumin, and grade of encephalopathy), except for age. Although majority of patients had undetermined etiology (32.5% in NAC group and 42.5% in control group), the second main cause was acute hepatitis E and drug or toxin-induced ALF. The mortality decreased to 28% with the use of NAC versus 53% in the control group (P = 0.023). The use of NAC was associated with shorter length of hospital stay in survived patients (P = 0.002). Moreover, the survival of patients was improved by NAC (P = 0.025). Also, drug-induced ALF showed improved outcome compared to other etiologies. Conclusion: The findings of the study recommend the use of NAC along with conventional treatments in patients with NAI-ALF in non-transplant centers while awaiting referrals and conclude the use of NAC as safe. PMID:28611340

  1. 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

  2. Immature mice are more susceptible than adult mice to acetaminophen-induced acute liver injury

    Science.gov (United States)

    Lu, Yan; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Chen, Xi; Xu, De-Xiang

    2017-01-01

    Acetaminophen (APAP) overdose induces acute liver injury. The aim of the present study was to analyze the difference of susceptibility between immature and adult mice to APAP-induced acute liver injury. Weanling immature and adult mice were injected with APAP (300 mg/kg). As expected, immature mice were more susceptible than adult mice to APAP-induced acute liver injury. APAP-evoked hepatic c-Jun N-terminal kinase phosphorylation was stronger in immature mice than in adult mice. Hepatic receptor-interacting protein (RIP)1 was obviously activated at APAP-exposed immature and adult mice. Interestingly, hepatic RIP3 activation was more obvious in APAP-treated immature mice than adult mice. Although there was no difference on hepatic GSH metabolic enzymes between immature and adult mice, immature mice were more susceptible than adult mice to APAP-induced hepatic GSH depletion. Of interest, immature mice expressed a much higher level of hepatic Cyp2e1 and Cyp3a11 mRNAs than adult mice. Correspondingly, immature mice expressed a higher level of hepatic CYP2E1, the key drug metabolic enzyme that metabolized APAP into the reactive metabolite NAPQI. These results suggest that a higher level of hepatic drug metabolic enzymes in immature mice than adult mice might contribute to the difference of susceptibility to APAP-induced acute liver injury. PMID:28205631

  3. Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

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    Fu-Chao Liu

    2016-01-01

    Full Text Available Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP- induced liver injury in a mice model. Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT and aspartate aminotransferase (AST levels, hepatic myeloperoxidase (MPO, malondialdehyde (MDA, glutathione (GSH, and superoxide dismutase (SOD activities, and liver histopathological changes were examined. The MAP kinases were also detected by western blotting. Results. Our results showed that tropisetron pretreatment significantly attenuated the acute elevations of the liver enzyme ALT level, hepatic MPO activity, and hepatocytes necrosis in a dose-dependent manner (0.3–10 mg/kg in APAP-induced hepatotoxicity mice. Tropisetron (1 and 3 mg/kg suppressed APAP-induced hepatic lipid peroxidation expression and alleviated GSH and SOD depletion. Administration of tropisetron also attenuated the phosphorylation of c-Jun-NH2-terminal protein kinase (JNK and extracellular signal-regulated kinase (ERK caused by APAP. Conclusion. Our data demonstrated that tropisetron’s hepatoprotective effect was in part correlated with the antioxidant, which were mediated via JNK and ERK pathways on acetaminophen-induced liver injury in mice.

  4. Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

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    Hyunseong Kim

    Full Text Available The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2 from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg in mice. Acetaminophen (APAP is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/- mice were injected with PLA2 once a day for five days and sacrificed 24 h (h after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST and alanine aminotransferase (ALT. PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

  5. Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver

    Science.gov (United States)

    Gamal, Wesam; Treskes, Philipp; Samuel, Kay; Sullivan, Gareth J.; Siller, Richard; Srsen, Vlastimil; Morgan, Katie; Bryans, Anna; Kozlowska, Ada; Koulovasilopoulos, Andreas; Underwood, Ian; Smith, Stewart; del-Pozo, Jorge; Moss, Sharon; Thompson, Alexandra Inés; Henderson, Neil C.; Hayes, Peter C.; Plevris, John N.; Bagnaninchi, Pierre-Olivier; Nelson, Leonard J.

    2017-01-01

    Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization. PMID:28134251

  6. Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver.

    Science.gov (United States)

    Gamal, Wesam; Treskes, Philipp; Samuel, Kay; Sullivan, Gareth J; Siller, Richard; Srsen, Vlastimil; Morgan, Katie; Bryans, Anna; Kozlowska, Ada; Koulovasilopoulos, Andreas; Underwood, Ian; Smith, Stewart; Del-Pozo, Jorge; Moss, Sharon; Thompson, Alexandra Inés; Henderson, Neil C; Hayes, Peter C; Plevris, John N; Bagnaninchi, Pierre-Olivier; Nelson, Leonard J

    2017-01-30

    Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization.

  7. [Activity of liver mitochondrial NAD+-dependent dehydrogenases of the krebs cycle in rats with acetaminophen-induced hepatitis developed under conditions of alimentary protein deficiency].

    Science.gov (United States)

    Voloshchuk, O N; Kopylchuk, G P

    2016-01-01

    Activity of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and the NAD(+)/NADН ratio were studied in the liver mitochondrial fraction of rats with toxic hepatitis induced by acetaminophen under conditions of alimentary protein deprivation. Acetaminophen-induced hepatitis was characterized by a decrease of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and malate dehydrogenase activities, while the mitochondrial NAD(+)/NADН ratio remained at the control level. Modeling of acetaminophen-induced hepatitis in rats with alimentary protein caused a more pronounced decrease in the activity of NAD(+)-dependent dehydrogenases studied and a 2.2-fold increase of the mitochondrial NAD(+)/NADН ratio. This suggests that alimentary protein deprivation potentiated drug-induced liver damage.

  8. Antioxidant and hepatoprotective potential of Pouteria campechiana on acetaminophen-induced hepatic toxicity in rats.

    Science.gov (United States)

    Aseervatham, G Smilin Bell; Sivasudha, T; Sasikumar, J M; Christabel, P Hephzibah; Jeyadevi, R; Ananth, D Arul

    2014-03-01

    Pouteria campechiana (Kunth) Baehni. is used as a remedy for coronary trouble, liver disorders, epilepsy, skin disease, and ulcer. Therefore, the present study aims to investigate the antioxidant and hepatoprotective effect of polyphenolic-rich P. campechiana fruit extract against acetaminophen-intoxicated rats. Total phenolic and flavonoid contents of egg fruit were estimated followed by the determination of antioxidant activities. Treatment with P. campechiana fruit extract effectively scavenged the free radicals in a concentration-dependent manner within the range of the given concentrations in all antioxidant models. The presence of polyphenolic compounds were confirmed by high-performance thin-layer chromatography (HPTLC). The animals were treated with acetaminophen (250 mg/kg body weight; p.o.) thrice at the interval of every 5 days after the administration of P. campechiana aqueous extract and silymarin (50 mg/kg). Acetaminophen treatment was found to trigger an oxidative stress in liver, leading to an increase of serum marker enzymes. However, treatment with P. campechiana fruit extract significantly reduced the elevated liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase) and increased the antioxidant enzymes (viz., superoxide dismutase and catalase) and glutathione indicating the effect of the extract in restoring the normal functional ability of hepatocytes. These results strongly suggest that P. campechiana fruit extract has strong antioxidant and significant hepatoprotective effect against acetaminophen-induced hepatotoxicity.

  9. Antioxidant and Hepatoprotective Efficiency of Selenium Nanoparticles Against Acetaminophen-Induced Hepatic Damage.

    Science.gov (United States)

    Amin, Kamal Adel; Hashem, Khalid Shaban; Alshehri, Fawziah Saleh; Awad, Said T; Hassan, Mohammed S

    2017-01-01

    Overdoses of acetaminophen (APAP), a famous and widely used drug, may have hepatotoxic effects. Nanoscience is a novel scientific discipline that provides specific tools for medical science problems including using nano trace elements in hepatic diseases. Our study aimed to assess the hepatoprotective role of selenium nanoparticles (Nano-Se) against APAP-induced hepatic injury. Twenty-four male rats were classified into three equal groups: a control group that received 0.9 % NaCl, an APAP-treated group (oral administration), and a group treated with Nano-Se (10-20 nm, intraperitoneal (i.p.) injection) and APAP (oral administration). APAP overdose induced significant elevations in liver function biomarkers, hepatic lipid peroxidation, hepatic catalase, and superoxide dismutase (SOD), decreased the reduced glutathione (GSH) content and glutathione reductase (GR) activity, and stimulated significant DNA damage in hepatocytes, compared to control rats. Nano-Se administration improved the hepatic antioxidant protection mechanism and decreased cellular sensitivity to DNA fragmentation. Nano-Se exhibits a protective effect against APAP-induced hepatotoxicity through improved liver function and oxidative stress mediated by catalase, SOD, and GSH and decreases hepatic DNA fragmentation, a hepatic biomarker of cell death. Nano-Se could be a novel hepatoprotective strategy to inhibit oxidative stress.

  10. Protective Effect of Sundarban Honey against Acetaminophen-Induced Acute Hepatonephrotoxicity in Rats

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    Rizwana Afroz

    2014-01-01

    Full Text Available Honey, a supersaturated natural product of honey bees, contains complex compounds with antioxidant properties and therefore has a wide a range of applications in both traditional and modern medicine. In the present study, the protective effects of Sundarban honey from Bangladesh against acetaminophen- (APAP- induced hepatotoxicity and nephrotoxicity in experimental rats were investigated. Adult male Wistar rats were pretreated with honey (5 g/kg for 4 weeks, followed by the induction of hepatotoxicity and nephrotoxicity via the oral administration of a single dose of APAP (2 g/kg. Organ damage was confirmed by measuring the elevation of serum alkaline phosphatase (ALP, alanine transaminase (ALT, aspartate transaminase (AST, total protein (TP, total bilirubin (TB, urea, creatinine, and malondialdehyde (MDA. Histopathological alterations observed in the livers and the kidneys further confirmed oxidative damage to these tissues. Animals pretreated with Sundarban honey showed significantly markedly reduced levels of all of the investigated parameters. In addition, Sundarban honey ameliorated the altered hepatic and renal morphology in APAP-treated rats. Overall, our findings indicate that Sundarban honey protects against APAP-induced acute hepatic and renal damage, which could be attributed to the honey’s antioxidant properties.

  11. Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity.

    Science.gov (United States)

    Wang, Kun-Peng; Bai, Yu; Wang, Jian; Zhang, Jin-Zhen

    2014-05-01

    Schisandra chinensis is a well-known traditional medicinal herb. Acetaminophen is a commonly used over-the-counter analgesic and overdose of acetaminophen was the most frequent cause of acute liver failure. However, no studies have demonstrated the role of Schisandra chinensis in acetaminophen-induced acute liver failure to the best of our knowledge. In this study, an acute liver injury model was established in mice using acetaminophen. The protective role of Schisandra chinensis was detected by histopathological analysis, and measurement of the serum transaminase levels and hepatic Cyp activity levels in the mouse model. Subsequently, hepatocytes were isolated from the livers of the mouse model. The cell cycle, apoptosis, mitochondrial membrane potential and reactive oxygen species were determined using flow cytometry. Cell proliferation and 26S proteasome activity were determined using spectrophotometry. Schisandra chinensis was found to resist acetaminophen-induced hepatotoxicity by protecting mitochondria and lysosomes and inhibiting the phosphor-c-Jun N-terminal kinase signaling pathway. These findings provide a novel application of Schisandra chinensis against acetaminophen-induced acute liver failure.

  12. 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.

  13. Outcomes of liver transplantation for paracetamol (acetaminophen)-induced hepatic failure.

    Science.gov (United States)

    Cooper, Sheldon C; Aldridge, Roland C; Shah, Tahir; Webb, Kerry; Nightingale, Peter; Paris, Sue; Gunson, Bridget K; Mutimer, David J; Neuberger, James M

    2009-10-01

    Paracetamol (acetaminophen) hepatotoxicity, whether due to intentional overdose or therapeutic misadventure, is an indication for liver transplantation in selected cases. However, there is a concern that long-term outcomes may be compromised by associated psychopathology that may predispose patients to further episodes of self-harm or poor treatment adherence. We therefore undertook a retrospective analysis of patients transplanted for paracetamol-induced fulminant hepatic failure (FHF) to determine their long-term outcomes, psychiatric problems, and compliance and whether these issues could be predicted from pretransplant information. Records from patients undergoing liver transplantation for paracetamol-associated liver failure in this unit and 2 comparison groups (patients undergoing liver replacement for FHF from other causes and for chronic liver diseases) were examined. Of 60 patients transplanted for paracetamol-induced FHF between 1989 and 2007, 44 (73%) survived to discharge. Currently, 35 patients (58%) are surviving at an average of 9 years post-transplantation. The incidence of psychiatric disease (principally depression) and 30-day mortality were greatest in the paracetamol group, but for those who survived 30 days, there was no difference in long-term survival rates between the groups. Adherence to follow-up appointments and compliance with immunosuppression were lowest in the paracetamol overdose group. Poor adherence was not predicted by any identifiable premorbid psychiatric conditions. Two patients grafted for paracetamol FHF died from self-harm (1 from suicide and 1 from alcoholic liver disease after 5 years). This study suggests that, notwithstanding the shortage of donor liver grafts, transplantation is an appropriate therapy in selected patients, although close follow-up is indicated.

  14. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats

    OpenAIRE

    Attalla Farag El-Kott, PhD; Mashael Mohammed Bin-Meferij, PhD

    2015-01-01

    Background: Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. Objective: To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. Methods: Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. Results: The treatment with Arctium lappa extract reduc...

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  17. Artificial liver support in pigs with acetaminophen-induced acute liver failure

    Science.gov (United States)

    He, Guo-Lin; Feng, Lei; Cai, Lei; Zhou, Chen-Jie; Cheng, Yuan; Jiang, Ze-Sheng; Pan, Ming-Xin; Gao, Yi

    2017-01-01

    AIM To establish a reversible porcine model of acute liver failure (ALF) and treat it with an artificial liver system. METHODS Sixteen pigs weighing 30-35 kg were chosen and administered with acetaminophen (APAP) to induce ALF. ALF pigs were then randomly assigned to either an experimental group (n = 11), in which a treatment procedure was performed, or a control group (n = 5). Treatment was started 20 h after APAP administration and continued for 8 h. Clinical manifestations of all animals, including liver and kidney functions, serum biochemical parameters and survival times were analyzed. RESULTS Twenty hours after APAP administration, the levels of serum aspartate aminotransferase, total bilirubin, creatinine and ammonia were significantly increased, while albumin levels were decreased (P < 0.05). Prothrombin time was found to be extended with progression of ALF. After continuous treatment for 8 h (at 28 h), aspartate aminotransferase, total bilirubin, creatinine, and ammonia showed a decrease in comparison with the control group (P < 0.05). A cross-section of livers revealed signs of vacuolar degeneration, nuclear fragmentation and dissolution. Concerning survival, porcine models in the treatment group survived for longer times with artificial liver system treatment (P < 0.05). CONCLUSION This model is reproducible and allows for quantitative evaluation of new liver systems, such as a bioartificial liver. The artificial liver system (ZHJ-3) is safe and effective for the APAP-induced porcine ALF model. PMID:28566885

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

    Science.gov (United States)

    González-Ponce, Herson Antonio; Martínez-Saldaña, María Consolación; Rincón-Sánchez, Ana Rosa; Sumaya-Martínez, María Teresa; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juárez, Fernando

    2016-01-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-l-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800 mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20 mmol/L APAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF. PMID:27782042

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

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    Herson Antonio González-Ponce

    2016-10-01

    Full Text Available Acetaminophen (APAP-induced acute liver failure (ALF is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC, the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800mg/kg/day, orally were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally. Rat hepatocyte cultures were exposed to 20mmol/LAPAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.

  20. Effect of N-Acetylcysteine on Mortality and Liver Transplantation Rate in Non-Acetaminophen-Induced Acute Liver Failure: A Multicenter Study.

    Science.gov (United States)

    Darweesh, Samar K; Ibrahim, Mona F; El-Tahawy, Mahmoud A

    2017-05-01

    Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF. In a prospective, multicenter, observational study, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were enrolled. NAC infusion (in empirical dose) was given as 150 mg/kg in 100 ml dextrose 5% over half an hour, then 70 mg/kg in 500 ml dextrose 5% over 4 h, then 70 mg/kg in 500 ml dextrose 5% over 16 h. Thereafter continuous infusion was administered over 24 h of 150 mg/kg in 500 ml dextrose 5% until up to two consecutive normal international normalized ratios (INRs) were obtained. Our endpoints were recovery, transplantation, or death. The primary outcome of the study was to assess reduction in mortality or liver transplantation. The secondary outcome was the evaluation of other clinical outcomes (length of ICU and hospital stays, organ system failure, and hepatic encephalopathy). The study included a total of 155 adults; the NAC group (n = 85) were given NAC between January 2011 to December 2013 and the control group (n = 70) were not given NAC and were included from files dating between 2010 and 2011. Both groups (before NAC) were comparable with regard to etiology, age, sex, smoking, presence of co-morbidities, encephalopathy, liver profile, and INR. The success rate (transplant-free survival) in the NAC group was 96.4%. While in the control group, 17 patients (23.3%) recovered and 53 (76.6%) did not recover, of these 37 (53.3%) had liver transplantation and 16 (23.3%) died (p < 0.01). The NAC group had significantly shorter hospital stays (p < 0.001), less encephalopathy (p = 0.02), and less bleeding (p < 0.01) than the control group. The control group reported a higher ICU admission (p = 0.01) rate and

  1. A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

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    Marco A De León-Nava

    Full Text Available We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group. Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT levels, CYP2E1 protein, interleukin (IL- 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group, whereas only one-third of uninfected animals exposed to acetaminophen (APAP group died. Uninfected (Control group and infected (Tc group mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

  2. A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

    Science.gov (United States)

    De León-Nava, Marco A; Álvarez-Delgado, Carolina; Donis-Maturano, Luis; Hernández-Ruiz, Joselin; Manjarrez-Reyna, Aaron N; Cruz-Avilés, Edgar; Leon-Cabrera, Sonia; Morales-Montor, Jorge; Fragoso, José M; Escobedo, Galileo

    2016-01-01

    We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients. PMID:27812602

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

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    Kenji Takemoto

    2014-01-01

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

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

    Science.gov (United States)

    Takemoto, Kenji; Hatano, Etsuro; Iwaisako, Keiko; Takeiri, Masatoshi; Noma, Naruto; Ohmae, Saori; Toriguchi, Kan; Tanabe, Kazutaka; Tanaka, Hirokazu; Seo, Satoru; Taura, Kojiro; Machida, Keigo; Takeda, Norihiko; Saji, Shigehira; Uemoto, Shinji; Asagiri, Masataka

    2014-01-01

    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. PMID:25349782

  5. 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

  6. Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice.

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    Rachel P L van Swelm

    Full Text Available Drug-induced liver injury (DILI is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP. Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw followed by 24 h urine collection. Doses of ≥275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT values (p<0.0001. Proteomic profiling resulted in the identification of 12 differentially excreted proteins in urine of mice with acute liver injury (p<0.001, including superoxide dismutase 1 (SOD1, carbonic anhydrase 3 (CA3 and calmodulin (CaM, as novel biomarkers for APAP-induced liver injury. Urinary levels of SOD1 and CA3 increased with rising plasma ALT levels, but urinary CaM was already present in mice treated with high dose of APAP without elevated plasma ALT levels. Importantly, we showed in human urine after APAP intoxication the presence of SOD1 and CA3, whereas both proteins were absent in control urine samples. Urinary concentrations of CaM were significantly increased and correlated well with plasma APAP concentrations (r = 0.97; p<0.0001 in human APAP intoxicants, who did not present with elevated plasma ALT levels. In conclusion, using this urinary proteomics approach we demonstrate CA3, SOD1 and, most importantly, CaM as potential human biomarkers for APAP-induced liver injury.

  7. Maintenance of hepatic glutathione homeostasis and prevention of acetaminophen-induced cataract in mice by L-cysteine prodrugs.

    Science.gov (United States)

    Rathbun, W B; Killen, C E; Holleschau, A M; Nagasawa, H T

    1996-05-03

    Administration of acetaminophen (ACP, 3.0 mmol/kg, i.p.) to beta-naphthoflavone-induced C57 BL/6 mice led to the formation of bilateral cataracts within 8 hr with a 71% incidence. The hepatic glutathione (GSH) levels were reduced 99% and lenticular GSH levels reduced 42% in cataractous mice. Cataract formation was completely prevented by the co-administration of the L-cysteine prodrugs 2(R, S)-methylthiazolidine-4(R)-carboxylic acid (MTCA) and 2(R, S)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA) in two divided i.p. doses totaling 4.5 mmol/kg. 2-Oxo-L-thiazolidine-4-carboxylic acid (OTCA) was nearly equipotent, yielding only one cataract in 16 mice, but D-ribose-L-cysteine (RibCys, 5/16) and N-acetyl-L-cysteine (NAC, 9/14) were much less effective. Hepatic and lenticular GSH were maintained at near normal levels by MTCA, PTCA and OTCA. These results suggest that maintenance of adequate cellular GSH levels in the presence of ACP protects against cataract induction.

  8. Protective effect of pioglitazone, a PPARγ agonist against acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Gupta, Gaurav; Krishna, Gopala; Chellappan, Dinesh Kumar; Gubbiyappa, Kumar Shiva; Candasamy, Mayuren; Dua, Kamal

    2014-08-01

    Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  10. Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

    NARCIS (Netherlands)

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Kuur, E.C. van der; Morava, E.; Wevers, R.A.; Augustijn, K.D.; Touw, D.J.; Sandel, M.H.; Masereeuw, R.; Russel, F.G.M.

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  12. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    El-Kott, Attalla Farag; Bin-Meferij, Mashael Mohammed

    2015-12-01

    Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. The treatment with Arctium lappa extract reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase in the acetaminophen group when compared with the control group. DNA fragments in the acetaminophen-injected group were also significantly increased (P Arctium lappa treatment (12.97±0.89 nmol/mg) when compared with the acetaminophen-treated-only group (12.97±0.89 nmol/mg). Histopathologic examination revealed that acetaminophen administration produced hepatic cell necrosis, infiltrate of lymphocytes, and vacuolation that were associated with the acetaminophen-treated animal group, but the degree of acetaminophen-induced hepatotoxicity was mediated by treatment with Arctium lappa extract. Arctium lappa can prevent most of the hepatic tissue damage caused by acetaminophen overdose in rats.

  13. Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2/ARE signaling pathway

    Science.gov (United States)

    Jiang, Yi-ming; Wang, Ying; Tan, Hua-sen; Yu, Tao; Fan, Xiao-mei; Chen, Pan; Zeng, Hang; Huang, Min; Bi, Hui-chang

    2016-01-01

    Aim: The nuclear factor erythroid 2-related factor 2 (NRF2) acts through the antioxidant response element (ARE) to regulate the expression of many detoxifying and antioxidant genes responsible for cytoprotective processes. We previously reported that Schisandrol B (SolB) isolated from Schisandra sphenanthera produced a protective effect against acetaminophen (APAP)-induced liver injury. In this study we investigated whether the NRF2/ARE signaling pathway was involved in this hepato-protective effect. Methods: Male C57BL/6 mice were treated with SolB (200 mg·kg−1·d−1, ig) for 3 d before injection of APAP (400 mg/kg, ip). Serum and liver tissue samples were collected 6 h later. The mRNA and protein expression were measured using qRT-PCR and Western blot assay, respectively. The activation of NRF2 was examined in HepG2 cells using luciferase reporter gene assay. Results: SolB pretreatment significantly alleviated the hepatic injury (large patchy necrosis and hyperemia of the hepatic sinus), the increase of serum AST, ALT levels and hepatic MDA contents, and the decrease of liver and mitochondrial glutathione levels in APAP-treated mice. Furthermore, SolB pretreatment significantly increased nuclear accumulation of NRF2 and increased hepatic expression of NRF2 downstream proteins, including GCLC, GSR, NQO1, GSTs, MRP2, MRP3 and MRP4 in APAP-treated mice. Moreover, treatment with SolB (2.5–20 μmol/L) dose-dependently increased the activity of NRF2 reporter gene in HepG2 cells. Conclusion: SolB exhibits a remarkable protective effect against APAP-induced hepatotoxicity, partially via activation of the NRF2/ARE pathway and regulation of NRF2 target genes, which induce detoxification and increase antioxidant capacity. PMID:26806302

  14. Elevated FABP1 serum levels are associated with poorer survival in acetaminophen-induced acute liver failure.

    Science.gov (United States)

    Karvellas, Constantine J; Speiser, Jaime L; Tremblay, Mélanie; Lee, William M; Rose, Christopher F

    2017-03-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality. Traditional prognostic scores lack sensitivity. Serum liver-type fatty acid binding protein (FABP1) early (day 1) or late (day 3-5) levels are associated with 21-day mortality in the absence of liver transplant. Serum samples from 198 APAP-ALF patients (nested case-control study with 99 survivors, 99 nonsurvivors) were analyzed by enzyme-linked immunosorbent assay with clinical data from the US Acute Liver Failure Study Group registry (1998-2014). APAP-ALF survivors had significantly lower serum FABP1 levels early (238.6 versus 690.8 ng/mL, P  350 ng/mL was associated with significantly higher risk of death at early (P = 0.0004) and late (P < 0.0001) time points. Increased serum FABP1 early (log FABP1 odds ratio = 1.31, P = 0.027) and late (log FABP1 odds ratio = 1.50, P = 0.005) were associated with significantly increased 21-day mortality after adjusting for significant covariates (Model for End-Stage Liver Disease, vasopressor use). Areas under the receiver operating characteristic curve for early and late multivariable models were 0.778 and 0.907, respectively. The area under the receiver operating characteristic curve of the King's College criteria (early, 0.552 alone, 0.711 with FABP1; late, 0.604 alone, 0.797 with FABP1) and the Acute Liver Failure Study Group prognostic index (early, 0.686 alone, 0.766 with FABP1; late, 0.711 alone, 0.815 with FABP1) significantly improved with the addition of FABP1 (P < 0.002 for all). In patients with APAP-ALF, FABP1 may have good potential to discriminate survivors from nonsurvivors and may improve models currently used in clinical practice; validation of FABP1 as a clinical prediction tool in APAP-ALF warrants further investigation. (Hepatology 2017;65:938-949). © 2016 by the American Association for the Study of Liver Diseases.

  15. Reversal of bioenergetics dysfunction by diphenyl diselenide is critical to protection against the acetaminophen-induced acute liver failure.

    Science.gov (United States)

    Carvalho, Nélson R; Tassi, Cintia C; Dobraschinski, Fernando; Amaral, Guilherme P; Zemolin, Ana P; Golombieski, Ronaldo M; Dalla Corte, Cristiane L; Franco, Jeferson L; Mauriz, José L; González-Gallego, Javier; Soares, Félix A

    2017-07-01

    Physiopathological conditions such as acute liver failure (ALF) induced by acetaminophen (APAP) can often impair the mitochondrial bioenergetics. Diphenyl diselenide [(PhSe)2] has been shown protects against APAP-induced ALF. The present study aimed to clarify the signaling mechanism involved in the protection of bioenergetics dysfunction associated with ALF-induced by APAP overdose. Mice received APAP (600mg/kg) or (PhSe)2 (15.6mg/kg) alone, or APAP+(PhSe)2, all the solutions were administered by the intraperitoneal (i.p.). Samples of liver, blood and liver mitochondria were collected at 2 and 4h after APAP administration. APAP-induced ALF was able to induce ALF by means of alteration on liver injury biomarkers, increased Nitrite and Nitrate levels and the impairment of oxidative phosphorylation capacity (OXPHOS). In parallel, APAP overdose promoted activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Heat shock protein 70 (HSP70) expression. (PhSe)2 was able to abolish the APAP-induced decline of OXPHOS and changes on the Nrf2-ARE pathway. In addition, (PhSe)2 elevated the levels of peroxisome proliferator-activated receptor-γ coactivator (PGC-1α), helping to restore the levels of nuclear respiratory factor 1 (NRF1) associated with mitochondrial biogenesis. In summary, the treatment with (PhSe)2 maintained mitochondrial function, promoted genes related to mitochondrial dynamic and demonstrating to play critical role in the modulation of cellular protective responses during ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats Transplante de hepatócitos recém-isolados em um modelo de hepatotoxicidade induzida por acetaminofeno em ratos

    Directory of Open Access Journals (Sweden)

    Daniela Rodrigues

    2012-12-01

    Full Text Available CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7 hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. RESULTS: Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. CONCLUSION: These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.CONTEXTO: O transplante de hepatócitos é uma modalidade terapêutica atrativa para doenças hepáticas como alternativa ao transplante hepático ortotópico. OBJETIVO: Investigar a factibilidade do uso de hepatócitos frescos isolados de ratos em um modelo de hepatotoxicidade induzida por paracetamol. MÉTODOS: Hepatócitos foram isolados de ratos Wistar machos e transplantados 24 horas após a administração de paracetamol em receptores fêmeas. As ratas receberam 1x10(7 hepatócitos ou tampão salina fosfato pela veia porta ou no baço e foram sacrificadas após 48 horas. RESULTADOS: Os níveis de alanina aminotransferase medidos durante o experimento não diferiram entre os grupos em nenhum momento. Análises moleculares e histológicas demonstraram a presença de hepatócitos no fígado dos animais transplantados pelo baço ou pela veia porta. CONCLUSÃO: Os dados indicam a factibilidade e eficácia do

  17. A novel upregulation of glutathione peroxidase 1 by knockout of liver-regenerating protein Reg3β aggravates acetaminophen-induced hepatic protein nitration.

    Science.gov (United States)

    Yun, Jun-Won; Lum, Krystal; Lei, Xin Gen

    2013-12-01

    Murine regenerating islet-derived 3β (Reg3β) represents a homologue of human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein and enhances mouse susceptibility to acetaminophen (APAP)-induced hepatotoxicity. Our objective was to determine if and how knockout of Reg3β (KO) affects APAP (300 mg/kg, ip)-mediated protein nitration in mouse liver. APAP injection produced greater levels of hepatic protein nitration in the KO than in the wild-type mice. Their elevated protein nitration was alleviated by a prior injection of recombinant mouse Reg3β protein and was associated with an accelerated depletion of the peroxynitrite (ONOO(-)) scavenger glutathione by an upregulated hepatic glutathione peroxidase-1 (GPX1) activity. The enhanced GPX1 production in the KO mice was mediated by an 85% rise (pnitration and a new biosynthesis control of GPX1 by a completely "unrelated" regenerating protein, Reg3β, via transcriptional activation of Scly in coping with hepatic protein nitration. Linking selenoproteins to tissue regeneration will have profound implications in understanding the mechanism of Se functions and physiological coordination of tissue regeneration with intracellular redox control. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. 扑热息痛肝损伤机制研究进展%Advances on mechanisms of acetaminophen-induced hepatic injury

    Institute of Scientific and Technical Information of China (English)

    顾兴丽; 孙继红; 季晖

    2009-01-01

    Acetaminophen(AAP) -induced hepatic injury is one of the common causes of drug-induced hepatic injury. Up to date, the mechanisms of AAP-induced hepatic injury are still incompletely understood. Recent advances suggest that reactive metabolite formation, glutathione depletion, alkylation of proteins, especially mitochondrial proteins and peroxynitrite formation are critical initiating events for the toxicity. This review will focus on more recent advances in mitochon- drial dysfunction after AAP overdose. Additional, oxi-dative stress and inflammatory mediators are also important for the overall outcome.%扑热息痛(AAP)肝损伤是药物性肝损伤的常见原因之一.但迄今为止,其肝损伤机制仍不完全清楚.最新研究进展指出活性代谢产物的形成、谷胱甘肽的耗竭、线粒体蛋白的烷化和过氧化亚硝酸盐的形成是主要原因.本文主要描述了AAP过量所致的线粒体功能异常的研究进展,另外也综述了氧化应激和炎症介质在扑热息痛肝损伤机制中的作用.

  19. Hepatoprotective and antioxidant effects of Azolla microphylla based gold nanoparticles against acetaminophen induced toxicity in a fresh water common carp fish (Cyprinus carpio L.

    Directory of Open Access Journals (Sweden)

    Selvaraj Kunjiappan

    2015-04-01

    Conclusion: Azolla microphylla phytochemically synthesized GNaP protects liver against oxidative damage and tissue damaging enzyme activities and could be used as an effective protector against acetaminophen-induced hepatic damage in fresh water common carp fish.

  20. Defensive nature of Sargassum polycystum (Brown alga)against acetaminophen-induced toxic hepatitis in rats: Role of drug metabolizing microsomal enzyme system, tumor necrosis factor-α and fate of liver cell structural integrity

    Institute of Scientific and Technical Information of China (English)

    H Balaji raghavendran; A Sathivel; T Devaki

    2006-01-01

    AIM: To assess the defensive nature of Sargassum polycystum (S. Polycystum) (Brown alga) against acetaminophen (AAP)-induced changes in drug metabolizing microsomal enzyme system, tumor necrosis factor (TNF-α)and fine structural features of the liver during toxic hepatitis in rats.METHODS: Male albino Wistar strain rats used for the study were randomly categorized into 4 groups. Group Ⅰ consisted of normal control rats fed with standard diet.Group Ⅱ rats were administered with acetaminophen (800 mg/kg body weight, intraperitoneally). Group Ⅲ rats were pre-treated with S. Polycystum extract alone.Group Ⅳ rats were orally pre-treated with S. Polycystum extract (200 mg/kg body weight for 21 d) prior to acetaminophen induction (800 mg/kg body weight,intraperitoneally). Serum separated and liver was excised and microsomal fraction was isolated for assaying cytochrome P450, NADPH Cyt P450 reductase and b5.Serum TNF-α was detected using ELISA. Fine structural features of liver were examined by transmission electron microscopy.RESULTS: Rats intoxicated with acetaminophen showed considerable impairment in the activities of drug metabolizing microsomal enzymes, such as cytochrome P450, NADPH Cyt P450 reductase and b5 when compared with the control rats. The rats intoxicated with acetaminophen also significantly triggered serum TNF-α when compared with the control rats. These severe alterations in the drug metabolizing enzymes were appreciably prevented in the rats pretreated with S. Polycystum. The rats pretreated with S. Polycystum showed considerable inhibition in the elevation of TNF-α compared to the rats intoxicated with acetaminophen. The electron microscopic observation showed considerable loss of structural integrity of the endoplasmic reticulum, lipid infiltration and ballooning of mitochondria in the acetaminophen-intoxicated rats,whereas the rats treated with S. Polycystum showed considerable protection against acetaminophen-induced alterations in

  1. Hepatoprotective Effect of Pretreatment with Thymus vulgaris Essential Oil in Experimental Model of Acetaminophen-Induced Injury.

    Science.gov (United States)

    Grespan, Renata; Aguiar, Rafael Pazinatto; Giubilei, Frederico Nunes; Fuso, Rafael Rocco; Damião, Marcio José; Silva, Expedito Leite; Mikcha, Jane Graton; Hernandes, Luzmarina; Bersani Amado, Ciomar; Cuman, Roberto Kenji Nakamura

    2014-01-01

    Acute liver damage caused by acetaminophen overdose is a significant clinical problem and could benefit from new therapeutic strategies. Objective. This study investigated the hepatoprotective effect of Thymus vulgaris essential oil (TEO), which is used popularly for various beneficial effects, such as its antiseptic, carminative, and antimicrobial effects. The hepatoprotective activity of TEO was determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity and subjected to histological analysis. In vitro antioxidant activity was evaluated by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•)-scavenging effects of TEO and TEO-induced lipid peroxidation. TEO reduced the levels of the serum marker enzymes AST, ALT, and ALP and MPO activity. The histopathological analysis indicated that TEO prevented acetaminophen-induced necrosis. The essential oil also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. These results suggest that TEO has hepatoprotective effects on acetaminophen-induced hepatic damage in mice.

  2. Hepatoprotective Effect of Pretreatment with Thymus vulgaris Essential Oil in Experimental Model of Acetaminophen-Induced Injury

    Directory of Open Access Journals (Sweden)

    Renata Grespan

    2014-01-01

    Full Text Available Acute liver damage caused by acetaminophen overdose is a significant clinical problem and could benefit from new therapeutic strategies. Objective. This study investigated the hepatoprotective effect of Thymus vulgaris essential oil (TEO, which is used popularly for various beneficial effects, such as its antiseptic, carminative, and antimicrobial effects. The hepatoprotective activity of TEO was determined by assessing serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and alkaline phosphatase (ALP in mice. Their livers were then used to determine myeloperoxidase (MPO enzyme activity and subjected to histological analysis. In vitro antioxidant activity was evaluated by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•-scavenging effects of TEO and TEO-induced lipid peroxidation. TEO reduced the levels of the serum marker enzymes AST, ALT, and ALP and MPO activity. The histopathological analysis indicated that TEO prevented acetaminophen-induced necrosis. The essential oil also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. These results suggest that TEO has hepatoprotective effects on acetaminophen-induced hepatic damage in mice.

  3. TRPM2 channels mediate acetaminophen-induced liver damage.

    Science.gov (United States)

    Kheradpezhouh, Ehsan; Ma, Linlin; Morphett, Arthur; Barritt, Greg J; Rychkov, Grigori Y

    2014-02-25

    Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca(2+) homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca(2+) concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca(2+) rise. Here we report that the channel responsible for Ca(2+) entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood concentration of liver enzymes and liver histology, is significantly diminished compared with wild-type mice. The presented data strongly suggest that TRPM2 channels are essential in the mechanism of acetaminophen-induced hepatocellular death.

  4. Prolonged acute hepatitis A mimicking autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Rintaro Mikata; Osamu Yokosuka; Fumio Imazeki; Kenichi Fukai; Tatsuo Kanda; Hiromitsu Saisho

    2005-01-01

    AIM: We report a case with a prolonged course of hepatitisA, with alanine aminotransferase (ALT) higher than 500 IU/Lfor more than 2 mo.METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive arti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out.RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCAproved to be effective.

  5. In vivo antioxidant activity of bark extract of Bixa orellana L. against acetaminophen- induced oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Smilin Bell Aseervatham G; Shamna R; Sangeetha B; Sasikumar JM

    2012-01-01

    Objective: To evaluate the in vivo activity of bark extract of Bixa orellana L. (B. orellana) against acetaminophen induced oxidative stress. Methods: In the present study, antioxidant activity ofB. orellana was evaluated by using normal and acetaminophen induced oxidative stressed rats at the dose of 100 mg/kg and 200 mg/kg p.o. oraly daily for 20 days. The animal's body weight was checked before and after treatment. Different biochemical parameters such as serum glutamate pyruvate transaminases, serum glutamate oxalo transaminases, alkaline phosphatase, total bilirubin, cholesterol, protein, lactate dehydrogenase, superoxide dismutase, catalase, ascorbic acid, lipid peroxide was performed. Histopathological analysis of the control and the hepatotoxicity induced rats were performed. Results: It was observed that the B. orellana bark extract showed significant protective activity against acetaminophen induced damage at 200 mg/kg dose level, while the 100 mg/kg dose showed moderate activity. Conclusions: From the result obtained in the present study suggest that B. orellana bark extract elicit protective activity through antioxidant activity on acetaminophen induced hepatic damage in rats.

  6. Acute pancreatitis in acute viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis.METHODS: We prospectively assessed the pancreatic involvement in patients with acute viral hepatitis who presented with severe abdomimanl pain.RESULTS: We studied 124 patients with acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven patients (5.65%) were diagnosed to have acute pancreatitis. All were young males. Five patients had pancreatitis in the first week and two in the fourth week after the onset of jaundice. The pancreatitis was mild and all had uneventful recovery from both pancreatitis and hepatitis on conservative treatment.The etiology of pancreatitis was hepatitis E virus in 4,hepatitis A virus in 2, and hepatitis B virus in 1 patient.One patient had biliary sludge along with HEV infection.The abdominal pain of remaining seventeen patients was attributed to stretching of Glisson's capsule.CONCLUSION: Acute pancreatitis occurs in 5.65% of patients with acute viral hepatitis, it is mild and recovers with conservative management.

  7. Protective Effect of Acacia nilotica (L. against Acetaminophen-Induced Hepatocellular Damage in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Narayanan Kannan

    2013-01-01

    Full Text Available The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT, Aspartate transaminase (AST, Alkaline phosphatase (ALP, total bilirubin, total protein, oxidative stress test (Lipid peroxidation, antioxidant parameter glutathione (GSH, and histopathological changes were examined. Our results show that the pretreatment with A. nilotica (250 mg/kg·bw orally revealed attenuation of serum activities of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by administration of acetaminophen. Further, pretreatment with extract elevated the total protein and GSH level and decreased the level of LPO. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by acetaminophen. The present study undoubtedly provides a proof that hepatoprotective action of A. nilotica extract may rely on its effect on reducing the oxidative stress in acetaminophen-induced hepatic damage in rat model.

  8. Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice.

    Science.gov (United States)

    Kawakami, Kayoko; Moritani, Chie; Uraji, Misugi; Fujita, Akiko; Kawakami, Koji; Hatanaka, Tadashi; Suzaki, Etsuko; Tsuboi, Seiji

    2017-03-01

    Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We found that rice peptides increased intracellular glutathione levels in human hepatoblastoma HepG2 cells. Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we investigated the protective effects of rice peptides on acetaminophen-induced hepatotoxicity in mice. ICR mice were orally administered rice peptides (0, 100 or 500 mg/kg) for seven days, followed by the induction of hepatotoxicity via intraperitoneal injection of acetaminophen (700 mg/kg). Pretreatment with rice peptides significantly prevented increases in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels and protected against hepatic glutathione depletion. The expression of γ-glutamylcysteine synthetase, a key regulatory enzyme in the synthesis of glutathione, was decreased by treatment with acetaminophen, albeit rice peptides treatment recovered its expression compared to that achieved treatment with acetaminophen. In addition, histopathological evaluation of the livers also revealed that rice peptides prevented acetaminophen-induced centrilobular necrosis. These results suggest that rice peptides increased intracellular glutathione levels and could protect against acetaminophen-induced hepatotoxicity in mice.

  9. Hepatoprotective Potential of Prosopis farcta Beans Extracts against Acetaminophen-induced Hepatotoxicity in Wister Rats

    OpenAIRE

    Akram Asadollahi; Hadi Sarir; Arash Omidi; Mohammad Bagher Montazar Torbati

    2014-01-01

    Background: Hepatotoxicity by acetaminophen is the most frequent cause of acute liver failure in many countries. Prosopis farcta beans extract (PFE) has some antioxidant property and may alleviate hepatotoxicity. Therefore, the aim of this study was to evaluate effects of PFE against acetaminophen-induced hepatotoxicity. Methods: Thirty-six male Wistar albino rats weighing 220 ± 30 g were distributed into six groups. Two groups were pretreated with PFE (50 and 75 mg/kg) for 7 days before ...

  10. Management of acute hepatitis B.

    Science.gov (United States)

    Shiffman, Mitchell L

    2010-02-01

    Acute hepatitis B virus (HBV) is a common cause of acute icteric hepatitis in adults. The vast majority of these patients resolve this acute infection and develop long-lasting immunity. In contrast, the vast majority of patients who develop chronic HBV have minimal symptoms and do not develop jaundice after becoming infected with HBV. These patients will frequently remain undiagnosed for years or decades. Approximately 1% of persons with acute HBV develop acute liver failure. Preventing acute HBV with vaccination is the best treatment. Although universal vaccination is now administered to newborns in many countries, the majority of adults have not been vaccinated and remain at risk. Because the majority of patients with acute HBV resolve this infection spontaneously, treatment with an oral anti-HBV agent is not necessary. However, the use of an oral anti-HBV agent is not unreasonable to use in a patient who is developing acute liver failure from severe acute HBV.

  11. Satkara (Citrus macroptera Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Sudip Paul

    2016-01-01

    Full Text Available Although Citrus macroptera (Rutaceae, an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

  12. Autoimmune hepatitis triggered by acute hepatitis A

    Institute of Scientific and Technical Information of China (English)

    Hiroto Tanaka; Hiroto Tujioka; Hiroki Ueda; Hiroko Hamagami; Youhei Kida; Masakazu Ichinose

    2005-01-01

    The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003.Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (×320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized,so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy,levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized.The present case was thus considered to represent AIH triggered by acute HA.

  13. Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice.

    Science.gov (United States)

    Maes, Michaël; Crespo Yanguas, Sara; Willebrords, Joost; Weemhoff, James L; da Silva, Tereza Cristina; Decrock, Elke; Lebofsky, Margitta; Pereira, Isabel Veloso Alves; Leybaert, Luc; Farhood, Anwar; Jaeschke, Hartmut; Cogliati, Bruno; Vinken, Mathieu

    2017-08-15

    Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen. Prior to this, in vitro testing was performed to confirm the specificity and efficacy of TAT-Gap24 and TAT-Gap19 in blocking connexin32 and connexin43 hemichannels, respectively. Subsequently, mice were overdosed with acetaminophen followed by treatment with TAT-Gap24 or TAT-Gap19 or a combination of both after 1.5h. Sampling was performed 3, 6, 24 and 48h following acetaminophen administration. Evaluation of the effects of connexin hemichannel inhibition was based on a series of clinically relevant read-outs, measurement of inflammatory cytokines and oxidative stress. Subsequent treatment of acetaminophen-overdosed mice with TAT-Gap19 only marginally affected liver injury. In contrast, a significant reduction in serum alanine aminotransferase activity was found upon administration of TAT-Gap24 to intoxicated animals. Furthermore, co-treatment of acetaminophen-overdosed mice with both peptides revealed an additive effect as even lower serum alanine aminotransferase activity was observed. Blocking of connexin32 or connexin43 hemichannels individually was found to decrease serum quantities of pro-inflammatory cytokines, while no effects were observed on the occurrence of hepatic oxidative stress. This study shows for the first time a role for connexin hemichannels in acetaminophen-induced acute liver failure. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Preventive and curative effects of Acalypha indica on acetaminophen-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    M Mathew

    2011-01-01

    Full Text Available Effect of ethanol extract of the leaves of Acalypha indica (Euphorbiaceae was investigated against acetaminophen-induced hepatic damage. Acetaminophen (paracetamol at the rate of 1 g/kg produced liver damage in rats as manifested by the significant (P<0.001 rise in serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT and alkaline phosphatase (ALP, compared to respective control values. Treatment of rats with acetaminophen led to a marked increase in lipid peroxidation as measured by malondialdehyde (MDA. This was associated with a significant reduction in superoxide dismutase (SOD and glutathione (GSH contents. Pretreatment of animals with the plant extract (100 mg/kg orally once daily for 5 days prevented (P<0.01 the acetaminophen-induced rise in serum transaminases (AST and ALT and ALP. Post treatment with five successive doses of the extract (100 mg/kg restricted the hepatic damage induced by the above said Paracetamol (P<0.001. Histological changes around the hepatic central vein were recovered by administration of the drug. Thus, it is evident that these biochemical and histological alterations resulting from acetaminophen administration were inhibited by pre and post treatment with A. indica leaf extract. One notable study of the study was the spontaneous recovery of liver damage within a week after stopping paracetamol. These results indicate that the crude ethanol extract of A. indica exhibits hepatoprotective action through antioxidant effect and validates the traditional use of the plant in hepatic dysfunction.

  15. Attenuation of uremia by orally feeding alpha-lipoic acid on acetaminophen induced uremic rats.

    Science.gov (United States)

    Pradhan, Shrabani; Mandal, Shreya; Roy, Suchismita; Mandal, Arpita; Das, Koushik; Nandi, Dilip K

    2013-04-01

    Uremia means excess nitrogenous waste products in the blood & their toxic effects. An acute acetaminophen (paracetamol, N-acetyl p-aminophenol; APAP) overdose may result into potentially fatal hepatic and renal necrosis in humans and experimental animals. The aims of this present study were to investigate the protective effect of alpha-lipoic acid (ALA) on oxidative stress & uremia on male albino rats induced by acetaminophen. The study was performed by 24 albino male Wister strain rats which were randomly divided into four groups: Group I, control - receives normal food and water, Groups II, III & IV receive acetaminophen interperitoneally at the dose of 500 mg/kg/day for 10 days, from 11th day Groups III & IV were treated with ALA at the dose of 5 mg & 10 mg/100 g/day for 15 days, respectively. After 25 days of treatment, it was observed that there was a significant increase in plasma urea, creatinine, sodium and malondialdehyde (MDA) levels (p < 0.05) but a significant decrease in super oxide dismutase (SOD) & catalase activity & potassium level in uremic group is compared with control group & there was a significant increase in SOD & catalase (p < 0.05) & a significant decrease in serum urea, creatinine & Na and MDA (p < 0.05) in Group III & Group IV is compared with Group II & significant changes were observed in high ALA dose group. In conclusion it was observed that the ALA has nephroprotective activities by biochemical observations against acetaminophen induced uremic rats.

  16. SIRS score reflects clinical features of non-acetaminophen-related acute liver failure with hepatic coma.

    Science.gov (United States)

    Miyake, Yasuhiro; Yasunaka, Tetsuya; Ikeda, Fusao; Takaki, Akinobu; Nouso, Kazuhiro; Yamamoto, Kazuhide

    2012-01-01

    In acetaminophen-induced acute liver failure (ALF), the hepatic coma grade worsens and mortality rates increase, as the number of systemic inflammatory response syndrome components fulfilled (SIRS score) increases. This study aimed to investigate the impact of SIRS score on clinical features of non-acetaminophen-related ALF. Ninety-nine patients with non-acetaminophen-related ALF with hepatic coma who did not undergo liver transplantation were investigated. Each patient was given a SIRS score of 0, 1, 2, 3 or 4 at the time of diagnosis. At the diagnosis of ALF with hepatic coma, with the increase of SIRS score, hepatic coma grade and prothrombin activity were deteriorated. After the diagnosis of ALF with hepatic coma, 25 patients (25%) developed acute respiratory distress syndrome (ARDS), 31 patients (31%) developed disseminated intravascular coagulation (DIC), and 21 patients (22%) developed acute renal failure (ARF). Thirty-eight patients (38%) developed MOF. With the increase of SIRS score, frequencies of the development of ARDS, DIC and MOF increased. ARF was more frequently developed in patients with a SIRS score of 2 or higher. Overall, 36 patients (36%) survived. Overall survival rate was 66% in 29 patients with a score of 0, 43% in 21 patients with a score of 1, 17% in 29 patients with a score of 2 and 15% in 20 patients with a score of 3 or 4. SIRS score will be useful for predicting not only the overall survival but also the development of complications such as ARDS, DIC and MOF in non-acetaminophen-related ALF with hepatic coma.

  17. Characteristics of acute hepatitis C

    Directory of Open Access Journals (Sweden)

    Mitrović Nikola

    2014-01-01

    Full Text Available Introduction. Acute hepatitis C most frequently develops after parenteral infection of hepatitis C virus. The disease often develops into chronic infection, although it can resolve spontaneously. Interferon alpha (INF-α is used in therapy, but still without precise treatment recommendations. Objective. The aim was to present characteristics of patients with acute hepatitis C and to assess effectiveness of using recombinant INF-α in therapy. Methods. Total of 55 patients with acute hepatitis C, hospitalized at the Clinic for Infectious Diseases in Belgrade from January 2005 to December 2012 were enrolled in this study. Forty-one patients were under follow-up over six months for evaluation of the development of the disease into a chronic infection and effectiveness of treatment with INF-α. Results. Eighty percent of patients were male of average age 29.6±8.6 years; in 61.8% patients intravenous drug abuse was determined as risk factor. Thirty patients (54.1% had no symptoms and 38.2% were icteric. Acute hepatitis C spontaneously resolved in 33.3% patients, while in the treated group 79.6% of patients completely recovered (p=0.006. Treatment success was 92.9% in the group of patients who started with treatment before the 45th day of disease, while in the patients who started treatment later the success rated 58.3% (p=0.037. Conclusion. Acute hepatitis C is most common in young male adults infected via injection drug abuse. The use of INF-α is effective in the treatment of the disease, and success of the treatment is more probable if treatment is started before the 45th day.

  18. Studies on acute hepatic insufficiency

    NARCIS (Netherlands)

    G.H. de Groot (Gerrit Harmen)

    1984-01-01

    textabstractAcute hepatic failure (AHF) is one of the most dramatic situations that a clinical physician can encounter. It is also one of the most frustating since death is the result in a large majority of the cases, despite all efforts of the medical and nursing staffs. Although a wide variety of

  19. patients with acute Icteric hepatitis

    African Journals Online (AJOL)

    *S. O. Ola, J. A. Otegbayo, G. N. Odaibo, O.-D. Olaleye and O. I. Olubuyide .... in Nigerian adults patients with acute ictcric hepatitis an d healthy adult at the .... lent in the course to chronicity. .... Corwin AL, Dai TC, Due DD, Suu PI, Van NT et al.

  20. Protective effects of red wine polyphenols and grape-seed proanthocyanidin extract on acetaminophen-induced liver injury

    Directory of Open Access Journals (Sweden)

    El-Sayed M. El-Sayed

    2014-11-01

    Full Text Available The present study was designed to examine the potential protective effects of red wine polyphenols (RWPs and grape seed proanthocyanidin extract (GSPE against acetaminophen-induced hepatotoxicity. Silymarin was used as a standard reference hepatoprotective agent. A single dose of acetaminophen (800 mg/kg, injected intraperitoneally to male rats, caused a significant increase in serum ALT, AST, alkaline phosphatase (ALP, bilirubin, total cholesterol (TC, triglycerides(TG, tumor necrosis factor alpha (TNF-α, and liver contents of thiobarbituric acid reactive substances (TBARS measured as malondialdehyde (MDA and nitric oxide (NO with significant decrease in serum albumin, HDL cholesterol, reduced glutathione (GSH and hepatic activities of catalase (CAT, superoxide dismutase (SOD and caspase-3 in liver tissue as compared with the control group. On the other hand, administration of each of GSPE (100 mg/kg/day, p.o., RWPs (40 mg/kg/day, p.o. and silymarin (100 mg/kg/day, p.o. for 15 consecutive days significantly ameliorated the liver injury which confirmed by the histopathological examination. It was concluded that RWPs and GSPE showed protective effects against acute acetaminophen hepatotoxicity where RWPs were more effective than GSPE; most probably through their antioxidant, anti-inflammatory and anti-apoptotic effects.

  1. Severe Acute Hepatitis B Treated With Entecavir.

    OpenAIRE

    De Socio, Giuseppe Vittorio Luigi; Sgrelli, Alessio; Tosti, Andrea; Baldelli, Franco

    2011-01-01

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. We present here a case of a 62-year-old man affected by severe acute hepatitis B with progressive worsening of clinical and hepatic function. The patient was treated with entecavir without critical side effects. We observed rapid clinical and laboratory improvements and the disappearance of hepatitis B surface antigen...

  2. Acetaminophen induces apoptosis in rat cortical neurons.

    Directory of Open Access Journals (Sweden)

    Inmaculada Posadas

    Full Text Available BACKGROUND: Acetaminophen (AAP is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to morbidity and mortality. Our hypothesis is that AAP causes direct neuronal toxicity contributing to the general AAP toxicity syndrome. METHODOLOGY/PRINCIPAL FINDINGS: We report that AAP causes direct toxicity on rat cortical neurons both in vitro and in vivo as measured by LDH release. We have found that AAP causes concentration-dependent neuronal death in vitro at concentrations (1 and 2 mM that are reached in human plasma during AAP overdose, and that are also reached in the cerebrospinal fluid of rats for 3 hours following i.p injection of AAP doses (250 and 500 mg/kg that are below those required to induce acute hepatic failure in rats. AAP also increases both neuronal cytochrome P450 isoform CYP2E1 enzymatic activity and protein levels as determined by Western blot, leading to neuronal death through mitochondrial-mediated mechanisms that involve cytochrome c release and caspase 3 activation. In addition, in vivo experiments show that i.p. AAP (250 and 500 mg/kg injection induces neuronal death in the rat cortex as measured by TUNEL, validating the in vitro data. CONCLUSIONS/SIGNIFICANCE: The data presented here establish, for the first time, a direct neurotoxic action by AAP both in vivo and in vitro in rats at doses below those required to produce hepatotoxicity and suggest that this neurotoxicity might be involved in the general toxic syndrome observed during patient APP overdose and, possibly, also when AAP doses in the upper dosing schedule are used, especially if other risk factors (moderate drinking, fasting, nutritional impairment are present.

  3. Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2005-01-01

    An increase in alpha-fetoprotein (AFP) following hepatic necrosis is considered indicative of hepatic regeneration. This study evaluated the prognostic value of serial AFP measurements in patients with severe acetaminophen-induced liver injury. Prospectively, serial measurements of AFP were...... performed in 239 patients with acetaminophen intoxication and a peak alanine aminotransferase (ALT) level above 1000 U/L. AFP was measured using an enzyme-linked immunoassay (EIA) with a detection limit below 0.4 microg/L. The optimum threshold of AFP to discriminate nonsurvivors was identified. An increase...... in AFP above 4 microg/L occurred in 158 (79%) of 201 survivors compared with 11 of 33 nonsurvivors (33%; P AFP occurred a mean of 1.0 days (range, -2 to +6 days) after peak ALT in survivors compared with 4.1 days (range, +2 to +7 days) in nonsurvivors (P

  4. Severe Acute Hepatitis B Treated with Entecavir

    OpenAIRE

    Giuseppe Vittorio Luigi De Socio; Alessio Sgrelli; Andrea Tosti; Franco Baldelli

    2011-01-01

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. We present here a case of a 62-year-old man affected by severe acute hepatitis B with progressive worsening of clinical and hepatic function. The patient was treated with entecavir without critical side effects. We observed rapid clinical and laboratory improvements and the disappearance of surface antigen (HBsAg). Th...

  5. Acute hepatitis with nontyphoidal salmonella and hepatitis E virus coinfection

    Directory of Open Access Journals (Sweden)

    Yu-Ting Kuo

    2014-09-01

    Full Text Available A 65-year-old Taiwanese man presented with dark urine for 5 days before admission to hospital and with fever on the 2nd day of admission to hospital. Laboratory studies showed acute hepatitis with hyperbilirubinemia. Acute hepatitis with nontyphoidal salmonella and hepatitis E virus coinfection was diagnosed. The fever subsided after treatment with ceftriaxone and cefepime. His serum bilirubin reached its peak value on the 3rd week after admission to hospital and then gradually returned to the normal range. To the best of our knowledge, acute hepatitis E coinfection with nontyphoidal salmonella has not been reported previously.

  6. Acute hepatic encephalopathy with diffuse cortical lesions

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)

    2001-07-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  7. Acute hepatitis C: Prospects and challenges

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    More than 170 million people worldwide have chronic hepatitis C. Acute hepatitis C is rarely diagnosed because it is commonly asymptomatic. Most infected patients are unaware of their condition until the symptoms of chronic infection manifest. Treatment of acute hepatitis C is something of a paradox because spontaneous resolution is possible and many patients do not have symptoms.However, several factors provide a rationale for treating patients who have acute hepatitis C. Compared with acute hepatitis C, chronic hepatitis C is associated with a worse prognosis, the need for more intensive treatment,longer treatment duration, and a decrease in successful treatment outcomes. Conversely, early intervention is associated with improved viral eradication, using a regimen that is better tolerated, less expensive, more convenient, and of shorter duration than the currently approved combination therapies for chronic hepatitis C.

  8. Acute pericarditis and renal failure complicating acute hepatitis A infection.

    Science.gov (United States)

    Beyazit, Yavuz; Guven, Gulay Sain; Kekilli, Murat; Koklu, Seyfettin; Yolcu, Omer Faruk; Shorbagi, Ali

    2006-01-01

    Hepatitis A infection may result in acute hepatitis, and rarely, fulminant hepatitis may ensue. Extrahepatic manifestations of hepatitis A are uncommon. The authors present the case of a 77-year-old male who had development of acute renal failure and pericarditis during the clinical course of acute hepatitis A infection. He died as a result of septic shock on the fifth day of hospitalization. To the best of our knowledge, this is the first report of both these rare and serious complications appearing in the same patient.

  9. Pediatric knowledge about acute viral hepatitis

    OpenAIRE

    Franca,Rita; Silva,Luciana; Melo, Maria Clotildes; Cavalcante,Suzy; Lima, Bruno; Rocha, Anita; Gomes, Cristiana; Franca, Mônica

    2004-01-01

    p.227-235 Knowledge about hepatotropic viruses is crucial for pediatricians because of the high prevalence of viral hepatitis during childhood. The multiplicity of hepatotropic viruses, the spectrum of acute and chronic infections, and the sequels of viral hepatitis result in a need for physicians to better understand the clinical and epidemiological context of patients with viral hepatitis, as well as the importance of prevention measures for hepatitis. A descriptive cross-sectional study...

  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

    2014-09-01

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

  11. Characteristics of hepatitis viruses among Egyptian children with acute hepatitis.

    Science.gov (United States)

    Youssef, Ahmed; Yano, Yoshihiko; El-Sayed Zaki, Maysaa; Utsumi, Takako; Hayashi, Yoshitake

    2013-04-01

    Hepatitis viral infection is hyperendemic in Egypt, western Asia and Africa. However, little is known about the status of hepatitis viruses among rural Egyptian children. Therefore, this study sought to examine the prevalence and characteristics of hepatitis viruses among symptomatic Egyptian children. Serological and molecular analyses of hepatitis viral infection were conducted in 33 children hospitalised at Mansoura University with symptomatic hepatic dysfunction (mean ± standard deviation age, 9.7±3.4 years; alanine aminotransferase level, 130±68 IU/ml). Eleven children (33%) were positive for anti-haemagglutination-IgM and were diagnosed with acute hepatitis A. Hepatitis B surface antigen (HBsAg) and anti‑hepatitis C virus (HCV) were detected in 9 (27%) and 7 (21%) children, respectively, indicating acute-on-chronic infection with hepatitis viruses. None of the children was positive for anti‑hepatitis B core antigen-IgM. Phylogenetic analysis confirmed that all HBVs belonged to genotype D (subgenotype D1) and that HCV belonged to genotypes 4a and 1g. HBV-DNA was detected in 9 children (27%) in the pre-S/S region and in 16 children (48%) in the core promoter/precore region. The Y134F amino acid mutation in the 'α' determinant region was detected in all of the patients. The A1762T/G1764A double mutation, and the T1846A and G1896A single mutations were common in children with occult HBV infection. In conclusion, hepatitis viral infection, including acute-on-chronic infection with HCV and HBV, is common in Egyptian children hospitalised with acute hepatitis.

  12. Chronic urticaria following acute hepatitis A.

    Science.gov (United States)

    Griffin, Paul M; Kevat, Dev A S; McCarthy, James S; Woods, Marion L

    2012-09-18

    Urticaria has a documented association with the prodromal phases of hepatitis A, B and, although still contentious, likely hepatitis C. Despite the documented association there are few actual reported cases of urticaria occurring with hepatitis A infection and in all of the cases reported so far the urticaria preceded the diagnosis of hepatitis A and was acute rather than chronic. We describe a case of urticaria occurring following acute infection with hepatitis A, which persisted beyond 6 weeks and therefore was by definition chronic. Although chronic urticaria has been reported to be associated with other forms of viral hepatitis, to the best of our knowledge this has not been reported previously with hepatitis A.

  13. Fulminant hepatic failure (FHF) due to acute hepatitis C.

    Science.gov (United States)

    Younis, Bilal Bin; Arshad, Rozina; Khurhsid, Saima; Masood, Junaid; Nazir, Farhan; Tahira, Maham

    2015-01-01

    Acute hepatitis C (HCV) infection has been identified as an important cause of fulminant hepatic failure (FHF), characterized by rapid deterioration of liver function from massive hepatic necrosis leading to encephalopathy and multi-organ failure. We admitted a female patient at Shalamar Hospital with jaundice, fever, encephalopathy and coagulopathy of short duration with no history of any comorbidity. Her hepatitis viral screen revealed positive anti HCV. Her viral loads were also high. A diagnosis of FHF due to acute HCV infection was made. Patient was treated conservatively and improved gradually. In summary, acute HCV can cause FHF and should be ruled out in patients with FHF of unknown cause in an endemic country for HCV like Pakistan.

  14. Severe Acute Hepatitis B Treated with Entecavir

    Directory of Open Access Journals (Sweden)

    Giuseppe Vittorio Luigi De Socio

    2011-03-01

    Full Text Available Hepatitis B virus (HBV infection constitutes a serious global health problem. Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. We present here a case of a 62-year-old man affected by severe acute hepatitis B with progressive worsening of clinical and hepatic function. The patient was treated with entecavir without critical side effects. We observed rapid clinical and laboratory improvements and the disappearance of surface antigen (HBsAg. The treatment with entecavir was protracted until 17th week when the antibody antiHBs (anti HBs appeared. Entecavir should be carefully considered for the treatment of severe acute hepatitis B cases.

  15. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  16. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  17. NNDSS - Table II. Hepatitis (viral, acute) C

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) C - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  18. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during the preceding...

  19. Protective Properties of Flavonoid Extract of Coagulated Tofu (Curdled Soy Milk Against Acetaminophen-Induced Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ndatsu Yakubu

    2016-01-01

    Full Text Available The total flavonoid contents of the various coagulated tofu and the hepatoprotective potential of all tofu flavonoid extracts were investigated. Tofu was prepared from locally sourced coagulants (steep water, alum, lemon, and lemon peel ash extract. Total flavonoid contents of all coagulated tofu were investigated as established in vitro flavonoid assay. The hepatoprotective activities of tofu flavonoid extracts against acetaminophen-induced hepatic cell toxicity in rats was also investigated in this study. The activity was analyzed by assessing the levels of serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and lactate dehydrogenase (LDH. The concentrations of the serum sugar, total protein, albumin, and cholesterol as well as prothrombin time (PT of experimental rats with histopathological analysis were also conducted. The range of the total flavonoid contents of tofu was 4.3-6.4 mg/g. Tofu flavonoid extracts significantly reduced the activities of serum AST, ALT, ALP, and LDH; total cholesterol, and sugar levels, but total protein and albumin concentrations increased compared to acetaminophen-intoxicated rats. Also, the prothrombin time prolongation of serum in acetaminophen intoxicated rats was reduced. Histology of the liver tissue demonstrated that tofu flavonoid extracts inhibited the acetaminophen-induced hepatic cell necrosis, decreased inflammatory cell infiltration and accelerated hepatocellular regeneration. Therefore, all tofus exhibited high total flavonoid contents, and the tofu supplement in human diets is highly recommended as it can be used as a functional food to prevent liver injuries.

  20. Hepatoprotective effects of Paeonia anomala against acetaminophen-induced cell damage through activation of anti-oxidant system

    Directory of Open Access Journals (Sweden)

    O Sarangerel

    2014-10-01

    Full Text Available Overdose of the analgesic and anti-pyretic acetaminophen causes a potentially fatal hepatic necrosis due to a high toxicity and depletion of cellular defense mechanisms. In the present work, the potential hepatoprotective effect of the fruit extract of Paeonia anomala against acetaminophen induced cell damages was evaluated in cultured HepG2 cells and compared to the root extract. The fruit extract showed a potent protection against acetaminophen induced cell death, while the root extract showed a weak protection. Particularly, the pre-treatment of lower doses of the fruit extract, 10 μg/ mL and 20 μg/mL, significantly enhanced cell viability. The level of total glutathione in HepG2 cells treated with the fruit extract prior to the treatment of 40 mM acetaminophen was enhanced, however, the root extract failed for this activity. In addition, activities of quinone reductase, glutathione peroxidase and glutathione reductase were increased and protein levels of glutathione peroxidase 1 and superoxide dismutase 1 were enhanced in the cells treated with 10-20 μg/mL of the fruit extract. Furthermore, the protein level of Nrf2, a crucial regulator for detoxifying and antioxidant systems, was increased by the fruit extract treatment. These results suggest that the fruit extract of P. anomala exerts protective effects against acetaminophen-induced toxicity through activation of key antioxidant systems.DOI: http://dx.doi.org/10.5564/mjc.v14i0.190 Mongolian Journal of Chemistry 14 (40, 2013, p.5-11

  1. PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS.

    Science.gov (United States)

    Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; Khattab, Alshaimaa

    2017-01-01

    Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential.

  2. Acetaminophen-induced liver injury: Implications for temporal homeostasis of lipid metabolism and eicosanoid signaling pathway.

    Science.gov (United States)

    Suciu, Maria; Gruia, Alexandra T; Nica, Dragos V; Azghadi, Seyed M R; Mic, Ani A; Mic, Felix A

    2015-12-05

    Acetaminophen is a commonly used drug that induces serious hepatotoxicity when overdosed, leading to increased levels of serum aminotransferases. However, little knowledge exists linking acetaminophen to liver free fatty acids and the eicosanoid-mediated signaling pathway. To this end, adult NMRI mice injected with a dose of 400 mg/kg acetaminophen were monitored for one week post-treatment. Consistent changes were observed in serum transaminases, profile of hepatic free fatty acids, expression of cyclooxygenase, elongase, lipogenesis, and lipolysis genes; as well as in expression patterns of cyclooxygenase-1 and -2 in the liver. Both linoleic acid and arachidonic acid--substrates in eicosanoid biosynthesis--were significantly influenced by overdose, and the latter peaked first among the free fatty acids examined here. There was a close similarity between the temporal dynamics of linoleic acid and aspartate aminotransferases. Moreover, serum transaminases were reduced by cyclooxygenase-2 inhibitors, but not by cyclooxygenase-1 inhibitors. Our results hence attest to the hazard of acetaminophen overdose on the temporal homeostasis of hepatic concentrations of free fatty acids and expression of key genes underlying liver lipid metabolism. There is also evidence for activation of a cyclooxygenase-mediated signaling pathway, especially the cyclooxygenase 2-prostanoid pathway, during acetaminophen-induced liver injury. Therefore, the results of the present study should provide valuable information to a wide audience, working to understand the health hazard of this drug and the implications of the eicosanoid signaling pathway in liver pathophysiology.

  3. Protective effects of pterostilbene against acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    El-Sayed, El-Sayed M; Mansour, Ahmed M; Nady, Mohamed E

    2015-01-01

    The present study was undertaken to evaluate the protective effect of pterostilbene against acetaminophen-induced hepatotoxicity. Silymarin was used as a standard hepatoprotective agent. A single dose of acetaminophen (800 mg/kg i.p.), injected to male rats, caused significant increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, total cholesterol, triglycerides, tumor necrosis factor alpha, and hepatic contents of malondialdehyde, nitric oxide, caspase-3, hydroxyproline, with significant decreases in serum HDL-cholesterol, total proteins, albumin, and hepatic activities of reduced glutathione, superoxide dismutase and catalase as compared with the control group. On the other hand, administration of each of pterostilbene (50 mg/kg, p.o.) and silymarin (100 mg/kg, p.o.) for 15 days before acetaminophen ameliorated liver function and oxidative stress parameters. Histopathological evidence confirmed the protection offered by pterostilbene from the tissue damage caused by acetaminophen. In conclusion, pterostilbene possesses multimechanistic hepatoprotective activity that can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic actions.

  4. Prophylactic and Therapeutic Potential of Acetyl-L-carnitine against Acetaminophen-Induced Hepatotoxicity in Mice.

    Science.gov (United States)

    Alotaibi, Salman A; Alanazi, Abdulrazaq; Bakheet, Saleh A; Alharbi, Naif O; Nagi, Mahmoud N

    2016-01-01

    Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen-induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes. Acetylcarnitine supplementation resulted in reversal of all biochemical parameters toward the control values. To explore the therapeutic effects of acetylcarnitine, mice were given a single dose of acetylcarnitine (0.5, 1, and 2 mmol/kg p.o.) 1.5 h after acetaminophen. Animals were sacrificed 6 h after acetaminophen. Acetylcarnitine administration resulted in partial reversal of liver injury only at 2 mmol/kg p.o. At equimolar doses, N-acetylcystiene was superior as therapeutic agent to acetylcarnitine. However, acetylcarnitine potentiated the effect of N-acetylcystiene in the treatment of acetaminophen toxicity.

  5. Severe Acute Hepatitis B Treated with Entecavir

    OpenAIRE

    Andrea Tosti; Alessio Sgrelli; Giuseppe Vittorio Luigi De Socio; Franco Baldelli

    2011-01-01

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. 
    Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. 
    Clinical and biochemical features of acute viral hepatitis | Spearman ...

    African Journals Online (AJOL)

    Clinical and biochemical features of acute viral hepatitis. ... systemic infection, presents with clinical manifestations relating directly to inflammation of the ... The most important causes of acute and chronic hepatitis are the five hepatotrophic ...

  6. Acute abdomen caused by brucellar hepatic abscess.

    Science.gov (United States)

    Ibis, Cem; Sezer, Atakan; Batman, Ali K; Baydar, Serkan; Eker, Alper; Unlu, Ercument; Kuloglu, Figen; Cakir, Bilge; Coskun, Irfan

    2007-10-01

    Brucellosis is a zoonotic infection that is transmitted from animals to humans by ingestion of infected food products, direct contact with an infected animal, or aerosol inhalation. The disease is endemic in many countries, including the Mediterranean basin, the Middle East, India, Mexico, Central and South America and, central and southwest Asia. Human brucellosis is a systemic infection with a wide clinical spectrum. Although hepatic involvement is very common during the course of chronic brucellosis, hepatic abscess is a very rare complication of Brucella infection. We present a case of hepatic abscess caused by Brucella, which resembled the clinical presentation of surgical acute abdomen.

  7. Albendazole-induced associated acute hepatitis and bicytopenia.

    Science.gov (United States)

    Ben Fredj, Nadia; Chaabane, Amel; Chadly, Zohra; Ben Fadhel, Najeh; Boughattas, Naceur A; Aouam, Karim

    2014-02-01

    Acute hepatitis induced by albendazole is rarely reported. We describe herein an original case of acute hepatitis associated with bicytopenia after albendazole intake. This paper is the first to describe a possible association of a hematologic disorder and acute hepatitis, both induced by albendazole therapy.

  8. Sestrin2 protects against acetaminophen-induced liver injury.

    Science.gov (United States)

    Kim, Seung Jung; Kim, Kyu Min; Yang, Ji Hye; Cho, Sam Seok; Kim, Ji Young; Park, Su Jung; Lee, Sang Kyu; Ku, Sae Kwang; Cho, Il Je; Ki, Sung Hwan

    2017-05-01

    Acetaminophen (APAP) overdose accounts for half of the cases of acute liver failure worldwide. We previously reported that Sestrin2 (Sesn2) protects against d-galactosamine/lipopolysaccharide-induced acute fulminant liver failure. In this study, we demonstrated that Sesn2 protects APAP-induced liver injury in mice, using a recombinant adenovirus encoding Sesn2 (Ad-Sesn2). First, we found that treatment of mice with toxic levels of APAP significantly reduced Sesn2 expression. Tail-vein injection with Ad-Sesn2 inhibited APAP-induced serum alanine aminotransferase and aspartate aminotransferase levels and markedly reduced hepatocyte degeneration and inflammatory cell infiltration. Additionally, APAP-induced glutathione depletion and reactive oxygen species generation were inhibited by Ad-Sesn2 treatment. Consistently, hepatic inflammatory gene expression and proinflammatory cytokine levels were also inhibited in Sesn2-infected mice, and we observed reduced APAP-mediated apoptotic signaling by terminal transferase-mediated dUTP nick-end labeling staining of the hepatic tissue. At a high dose of APAP, the mortality rate of Ad-Sesn2-infected mice was significantly lower than that of control mice. Furthermore, Sesn2 prevented APAP-induced damage through suppression of downstream mitogen-activated protein kinase pathway activation. Therefore, Sesn2 exerted a protective effect against APAP-induced acute liver damage by inhibiting oxidative stress and proinflammatory signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Translational biomarkers of acetaminophen-induced acute liver injury.

    Science.gov (United States)

    Beger, Richard D; Bhattacharyya, Sudeepa; Yang, Xi; Gill, Pritmohinder S; Schnackenberg, Laura K; Sun, Jinchun; James, Laura P

    2015-09-01

    Acetaminophen (APAP) is a commonly used analgesic drug that can cause liver injury, liver necrosis and liver failure. APAP-induced liver injury is associated with glutathione depletion, the formation of APAP protein adducts, the generation of reactive oxygen and nitrogen species and mitochondrial injury. The systems biology omics technologies (transcriptomics, proteomics and metabolomics) have been used to discover potential translational biomarkers of liver injury. The following review provides a summary of the systems biology discovery process, analytical validation of biomarkers and translation of omics biomarkers from the nonclinical to clinical setting in APAP-induced liver injury.

  11. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim; Poulsen, Henrik Enghusen

    2002-01-01

    The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were...

  12. Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Nesreen E.M. Mohammed

    2016-11-01

    Conclusion: Amlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.

  13. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Ivan Kraus

    2001-01-01

    Full Text Available Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  14. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

    OpenAIRE

    Ivan Kraus; Dinko Vitezic

    2001-01-01

    Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  15. [Morphological characteristic of rats’ kidneys under the conditions of acetaminophen-induced nephrotoxicity against the background alimentary deprivation of protein

    Directory of Open Access Journals (Sweden)

    Kopylchuk G.P.

    2015-09-01

    Full Text Available Background. Acetaminophen is known as inducer of acute hepatotoxicity. Extrahepatic manifestations of acetaminophen toxicity are poorly understood in particular its nephrotoxicity. Objective. The purpose of this study was the morphological characteristic of rat kidneys under the conditions of acetaminophen-induced nephrotoxicity on the background of alimentary deprivation of protein. Methods. Аfter administration of the toxic dose of acetaminophen and maintenance of rats on a different regimen of protein nutrition their kidneys were sectioned and stained with hematoxylin and eosin according to a standard technique. Results. It was estimated, that in rats maintained during long period of time under the conditions of alimentary deprivation of protein, and in rats injected with toxic dose of acetaminophen morphological changes of kidney were not observed. Administration of acetaminophen on the background of previous protein deficiency causes the pathological changes of kidney morphology with papillary necrosis as a key sign. Conclusion. Alimentary deprivation of protein in case of acetaminophen injection is the critical factor for the impairment of structural integrity of kidney tissue with its subsequent dysfunction. Citation: Kopylchuk GP, Voloshchuk ON, Buchkovskaia IM, Davydenko IS. [Morphological characteristic of rats’ kidneys under the conditions of acetaminophen-induced nephrotoxicity against the background alimentary deprivation of protein]. Morphologia. 2015;9(3:28-30. Russian.

  16. Impaired plasma lipid profiles in acute hepatitis

    Directory of Open Access Journals (Sweden)

    Wang Yongzhong

    2010-01-01

    Full Text Available Abstract The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Patients' blood samples were collected at both the debut and recovery of diseases. Thirty sex and age matched normal subjects were included as controls. Plasma total triglycerides (TG, total cholesterol, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C, apolipoprotein AI (ApoAI, apolipoprotein B (ApoB, lipoprotein (a (Lp(a, blood coagulation status including prothrombin complex activity and activated partial tromboplastin time (APTT, and hepatic functions were determined by the automatic biochemical analytical instrument. It demonstrated that plasma levels of total cholesterol, HDL-C and apoAI were significantly lower in the patients at the acute phase of hepatitis than those in normal subjects, whereas plasma levels of TG and LDL-C were obviously higher in the patients than in normal subjects (P

  17. Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats.

    Science.gov (United States)

    Reshi, Mohd Salim; Shrivastava, Sadhana; Jaswal, Amita; Sinha, Neelu; Uthra, Chhavi; Shukla, Sangeeta

    2017-04-04

    Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Ischaemic Markers in Acute Hepatic Injury

    Science.gov (United States)

    Jena, Sushanta Kumar; Nanda, Rachita; Mangaraj, Manaswini; Nayak, Parsuram

    2016-01-01

    Introduction Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT-LDH ratio and ALT-LDH index have been suggested for its detection at early stage. Aim To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. Materials and Methods Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1st day and 7th day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. Result Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1st day of admission. ALT-LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7th day registered a rise in comparison to the 1st day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. Conclusion Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID:27190791

  19. Factors influencing the severity of acute viral hepatitis A

    Science.gov (United States)

    Kim, Joo Il; Jung, Young Kul; Kwon, Oh Sang; Kim, Yeon Suk; Ku, Yang Suh; Choi, Duck Joo; Kim, Ju Hyun

    2010-01-01

    Background/Aims Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. Methods We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups. Results The incidence of fulminant hepatitis was 1.4% (10/713) in patients with acute hepatitis A. Thirty-three (4.6%) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. Conclusions While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection. PMID:20924212

  1. Case of acute hepatitis E with concomitant signs of autoimmunity

    OpenAIRE

    Vieira, Catarina Lima; Baldaia, Cilénia; Fatela, Narcisa; Ramalho,Fernando; Cardoso, Carlos

    2013-01-01

    Sporadic cases of acute viral hepatitis E have been described in developed countries, despite the more common occurrence in endemic areas and developing countries. We present the case of a 58 years old Portuguese female, with no epidemiological relevant factors, admitted with acute hepatitis with positive anti-nuclear antibodies, anti-smooth muscle antibody and high serum gamma globulin (> 1.5 fold increase). Serologies for hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein-Barr...

  2. Frequency of Acute Hepatitis Following Acute Paraphenylene Diamine Intoxication.

    Science.gov (United States)

    Ishtiaq, Rizwan; Shafiq, Sadaf; Imran, Ali; Masroor Ali, Qazi; Khan, Raheel; Tariq, Hassan; Ishtiaq, Daniyal

    2017-04-21

    Paraphenylene diamine (PPD) ingestion is manifesting as one of the more common ways of committing suicide in Southern Punjab, Pakistan, especially Bahawalpur. PPD is an ingredient of a compound commonly known "Kala Pathar" which means "Black Stone" in Urdu. It is readily available in the market at low cost and is used to dye hair and fur. Its intoxication inhibits cellular oxidation and affects the muscles causing rhabdomyolysis. This leads to myoglobinuria followed by renal failure and edema of face and throat resulting in respiratory difficulty. Very little is known about the impact of PPD intoxication on liver tissue. The purpose of the study was to find out the frequency of acute hepatitis following PPD intoxication. We reviewed the medical records of 109 patients with PPD intoxication admitted to Medical Unit-2, Bahawalpur Victoria Hospital from January 1, 2015, to June 30, 2015, in a descriptive, cross-sectional study. We noted the frequency of acute hepatitis and other complications, and we recorded the demographic features, clinical features, and outcomes of these patients. Our study included 32 men (29%) and 77 women (71%). The mean age was 22 ± 3.4 years, and most patients were young women aged 15 to 24 years. Suicidal ingestion was the leading cause of admission for 101 patients (93%). The most common clinical presentation was cervicofacial edema (95%), throat pain (88%), dysphonia (95%), cola-colored urine (100%), and oliguria (95%). Rhabdomyolysis (86%), acute hepatitis (51%), and acute renal failure (63%) were the most common clinical conditions following poisoning. Overall mortality was noted in 39 patients (36%) while all other patients achieved complete clinical recovery (64%). In patients with mortality, 20 of 39 (51%) developed acute hepatitis. Most patients (95%) in our study underwent tracheostomy. The frequency of acute hepatitis in PPD intoxication is high in this population, especially in young women. Measures need to be instituted

  3. Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Yamada, S; Murawaki, Y; Kawasaki, H

    1993-09-14

    The preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats was examined by histological and biochemical analysis. Acetaminophen at a dose of 750 mg/kg was administered to male Wistar rats with or without pretreatment with 50 mg/kg of gomisin A. Gomisin A inhibited not only the elevation of serum aminotransferase activity and hepatic lipoperoxides content, characteristic of acetaminophen administration, but also the appearance of histological changes such as degeneration and necrosis of hepatocytes. However, gomisin A did not affect the decrease in liver glutathione content. These results suggest that gomisin A protects the liver from injury after administration of acetaminophen through the suppression of lipid peroxidation.

  4. Cerebral edema associated with acute hepatic failure.

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    Fujiwara,Masachika

    1985-02-01

    Full Text Available The clinicopathological findings of cerebral edema were investigated in patients with acute hepatic failure autopsied at Okayama University Hospital between 1970 and 1980 retrospectively. Nine (64% of 14 hepatic failure cases were found to have cerebral edema during a post-mortem examination of the brain. Clinical features of the patients with cerebral edema were not significantly different from those of the patients without cerebral edema. However, general convulsions were observed more frequently in patients later found to have cerebral edema. Moreover, the length of time from deep coma to death was much shorter in the brain edema cases with cerebral herniation than without herniation.

  5. Acute Brucellar Hepatitis: Report of Two Cases

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    Keramat

    2015-05-01

    Full Text Available Introduction Brucellosis is a common zoonotic disease which has a wide spectrum of clinical manifestations and complications in humans. Brucellosis is an endemic disease in Iran. The aim of this case report was to introduce acute hepatitis as a rare complication of acute brucellosis. Case Presentation First case, a 25-year-old man, who complained from fever, chillness, nocturnal sweating, nausea, vomiting, jaundice, and right upper quadrant pain, and was admitted to the hospital. Laboratory tests showed a five-fold increase in alanine aminotransferase and aspartate aminotransferase levels, and increased total and direct bilirubin and alkaline phosphatase levels. Second case, a 63-year-old man, who complained from fever, chillness, weight loss, malaise and nocturnal sweating, and was admitted to the hospital. Laboratory tests showed an eight-fold increase in alanine aminotransferase and aspartate aminotransferase levels, and increased total and direct bilirubin and alkaline phosphatase levels. The patient had jaundice at the third day of admission. The results of seroagglutination tests, Wright and 2-mercaptoethanol (2ME were positive for both patients. The patients were diagnosed as having acute brucella hepatitis and were treated with standard regimen of anti-brucella drugs and improved completely after six weeks of treatment. Conclusions Brucellosis must be considered in the differential diagnosis of acute hepatitis in patients with jaundice and fever manifestations especially if there is a history of unpasteurized dairy products ingestion and life in endemic areas because early diagnosis and treatment of the patient can decrease complications and mortality rate.

  6. Acute hepatitis C in patients receiving hemodialysis.

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    Griveas, I; Germanidis, G; Visvardis, G; Morice, Y; Perelson, A S; Pawlotsky, J M; Papadopoulou, D

    2007-01-01

    Hepatitis C virus (HCV) infection is frequent in patients with end-stage renal disease treated by chronic dialysis, with a prevalence varying from 10-65% according to the geographical data. The prevalence is significantly associated with the duration of dialysis and the number of transfused blood products[1,2] and has dramatically declined with efficient blood screening.[3] We studied patients with acute HCV infection in a dialysis unit. The diagnosis was based on both anti-HCV detection and HCV-RNA detection. Other virological tools including HCV genotype determination was also used to tailor treatment to the individual patient and determine its efficacy for a one-year follow-up period. Seventeen patients (7 male and 10 female, mean age: 63.7 +/- 11.6 SD) with acute hepatitis C were enrolled to our study. All of them were followed up for a period of one year after the diagnosis was established. Phylogenetic analysis distinguished two separate HCV subtypes 1b, which were both responsible for this acute infection (see Figure 1). These types did not differ in their behavior on the clinical situation of our patients, as confirmed by the fact that in both groups of patients, there was only one patient who presented with acute illness. Six patients of our study group, three months after the acute infection, received pegylated interferon (Peg-IFNa2a) 135 mug for a six-month period. Four of them responded very well to therapy and at the first determination HCV RNA was below the cutoff point. One of our patients with very high HCV levels (HCV RNA > 50,000,000 IU/mL), despite receiving the same therapy, did not respond well and developed cirrhosis. In conclusion, it is clear from our experience that better information is needed about the current incidence, prevalence, and risk factors for HCV infection in dialysis patients. Algorithms for the diagnosis and management of hepatitis C should be developed by academic societies. Routine screening for hepatitis C also would allow

  7. Alverine citrate induced acute hepatitis

    Institute of Scientific and Technical Information of China (English)

    Mehmet Arhan; Seyfettin K(o)klü; Aydln S K(o)ksal; (O)mer F Yolcu; Senem Koruk; Irfan Koruk; Ertugrul Kayacetin

    2004-01-01

    Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent. A 34-year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening. Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment.Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case, several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity.

  8. Severe Acute Hepatitis B Treated with Entecavir

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    Andrea Tosti

    2011-01-01

    Full Text Available

    Hepatitis B virus (HBV infection constitutes a serious global health problem. 
    Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. 
    We present here a case of a 62-year-old man affected by severe acute hepatitis B with progressive worsening of clinical and hepatic function. 
    The patient was treated with entecavir without critical side effects. 
    We observed rapid clinical and laboratory improvements and the disappearance of surface antigen (HBsAg. 
    The treatment with entecavir was protracted until 17th week when the antibody antiHBs (anti HBs appeared. 
    Entecavir should be carefully considered for the treatment of severe acute hepatitis B cases.

  9. Clearance of HCV RNA following acute hepatitis A superinfection.

    Science.gov (United States)

    Cacopardo, B; Nunnari, G; Nigro, L

    2009-05-01

    A transient reduction of hepatitis C virus replication during the course of acute hepatitis A virus infection has already been reported in the literature. The present study reports the case study of a subject with chronic hepatitis due to hepatitis C virus who went on to develop an acute hepatitis A. From the early onset of acute disease, hepatitis C virus ribonucleic acid became undetectable. Following recovery from acute hepatitis, alanine amino-transferase levels became persistently normal and liver biopsy revealed a reduction in the Knodell histological activity index score. Hepatitis C virus ribonucleic acid clearance was maintained up to 4 years after the onset of acute hepatitis A. During the course of the acute disease, a sharp increase in interferon gamma levels was detected in serum and in the supernatant of both unstimulated and phytoemagglutinin/lipopolysaccharide-stimulated peripheral blood mononuclear cells. Interferon gamma levels were still high 3 months later. We hypothesize that acute hepatitis A virus superinfection during the course of chronic hepatitis C may lead to hepatitis C virus ribonucleic acid clearance through an immunological mechanism related to interferon gamma production.

  10. Clindamycin-induced acute cholestatic hepatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  11. Acute pancreatitis, acute hepatitis and acute renal failure favourably resolved in two renal transplant recipients.

    Science.gov (United States)

    Voiculescu, Mihai; Ionescu, Camelia; Ismail, Gener; Mandache, Eugen; Hortopan, Monica; Constantinescu, Ileana; Iliescu, Olguta

    2003-03-01

    Renal transplantation is often associated with severe complications. Except for acute rejection, infections and toxicity of immunosuppressive treatment are the most frequent problems observed after transplantation. Infections with hepatic viruses (HBV, HDV, HCV, HGV) and cytomegalic virus (CMV) are the main infectious complications after renal transplantation. Cyclosporine toxicity is not unusual for a patient with renal transplantation and is even more frequent for patients with hepatic impairment due to viral infections. The subjects of this report are two renal transplant recipients with acute pancreatitis, severe hepatitis and acute renal failure on graft, receiving immunosuppressive therapy for maintaining renal graft function

  12. Acute hepatitis due to dengue virus in a chronic hepatitis patient

    OpenAIRE

    Souza, L J; Coelho, J.M.C. de O.; Silva,E. J.; Abukater,M.; Almeida,F.C.R.; A. S. Fonte; L.A Souza

    2008-01-01

    We present a case of acute hepatitis caused by dengue virus, with a significant increase in aspartate transferase and alanine transferase levels in a chronic hepatitis patient attended at the Cane Sugar Planters Hospital of Campos dos Goytacazes, RJ.

  13. Acute hepatitis due to brucellosis: case report

    Directory of Open Access Journals (Sweden)

    Nevil AYKIN

    2009-06-01

    Full Text Available Brucella infection is a systemic disease. It rarely causes local infections like hepatitis in gastrointestinal system. In this article we would like to present an acute hepatitis case related to brucella infection that followed up in our clinic. A male, 30 year-old patient hospitalized due to common muscle pain, high fever and vomiting. During the physical examination the patient’s skin, scleras and mucosal membranes were icteric, the liver was 2-3 cm palpable and tender. Laboratory findings were as follows: AST:1190 U/L; ALT:715 U/L; GGT:961 U/L; ALP:369 U/L; total bilirubin:4.6 mg/dL; direct bilirubin:2.1 mg/dL. Viral markers were found to be negative. We started treatment with streptomicine and doxicycline since, the patient’s standard brucella tube agglutination test was positive (1/60 and brucella spp produced in his blood culture. From the second day of the treatment, we started to get clinical response. On the 17th day of the treatment, he discharged from the hospital because ALT, AST and bilirubine level were found normal and his treatment was completed to the 8 weeks. Brucella is continuing to be an important health problem especially who live in surrounding countryside and have to keep in mind in the differential diagnosis of the acute hepatitis.

  14. Histological and immunohistochemical features in fatal acute fulminant hepatitis E

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    Vinita Agrawal

    2012-01-01

    Full Text Available Background: Hepatitis E is being increasingly recognized as an emerging infection in developed countries. Data on histological findings and nature of inflammatory cell infiltrate in liver in this disease are quite sparse. Aims: This study was planned to study the histological features and the type of inflammatory infiltrate in liver biopsies of patients with acute fulminant hepatitis E. Materials and Methods: We retrieved postmortem liver biopsies of 11 Indian patients with fulminant hepatitis E, and compared these with biopsies from seven patients with fulminant hepatitis B. Results : Biopsies from acute fulminant hepatitis E showed varying degrees of hepatocyte necrosis, mixed portal and lobular inflammation, accompanied by bile ductular proliferation, lymphocytic cholangitis, Kupffer cell prominence, cholestasis, apoptotic bodies, pseudo-rosette formation, steatosis, and presence of plasma cells in portal tracts. Interface hepatitis was more frequent in acute hepatitis B than in acute hepatitis E (100% vs 20%; P<0.05. These findings differ from those reported in cases with autochthonous hepatitis E in Europe. On immunohistochemistry, lymphocyte infiltrate consisted predominantly of CD3 + T cells in both hepatitis E and hepatitis B; these cells contained a predominant cytotoxic (CD8 + cell subpopulation in 81.8% of cases with hepatitis E and in 50% of cases with hepatitis B. Conclusion: Our findings suggest that histological changes in HEV infection may vary with geographical location because of prevalent HEV genotypes, and that CD8 + lymphocytes play a role in HEV-induced liver injury.

  15. Serotonin deficiency exacerbates acetaminophen-induced liver toxicity in mice.

    Science.gov (United States)

    Zhang, Jingyao; Song, Sidong; Pang, Qing; Zhang, Ruiyao; Zhou, Lei; Liu, Sushun; Meng, Fandi; Wu, Qifei; Liu, Chang

    2015-01-29

    Acetaminophen (APAP) overdose is a major cause of acute liver failure. Peripheral 5-hydroxytryptamine (serotonin, 5-HT) is a cytoprotective neurotransmitter which is also involved in the hepatic physiological and pathological process. This study seeks to investigate the mechanisms involved in APAP-induced hepatotoxicity, as well as the role of 5-HT in the liver's response to APAP toxicity. We induced APAP hepatotoxicity in mice either sufficient of serotonin (wild-type mice and TPH1-/- plus 5- Hydroxytryptophan (5-HTP)) or lacking peripheral serotonin (Tph1-/- and wild-type mice plus p-chlorophenylalanine (PCPA)). Mice with sufficient 5-HT exposed to acetaminophen have a significantly lower mortality rate and a better outcome compared with mice deficient of 5-HT. This difference is at least partially attributable to a decreased level of inflammation, oxidative stress and endoplasmic reticulum (ER) stress, Glutathione (GSH) depletion, peroxynitrite formation, hepatocyte apoptosis, elevated hepatocyte proliferation, activation of 5-HT2B receptor, less activated c-Jun NH₂-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1α in the mice sufficient of 5-HT versus mice deficient of 5-HT. We thus propose a physiological function of serotonin that serotonin could ameliorate APAP-induced liver injury mainly through inhibiting hepatocyte apoptosis ER stress and promoting liver regeneration.

  16. Acute Brucella Hepatitis in an Urban Patient

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    Seyed Moayed Alavian

    2009-11-01

    Full Text Available A 35-year-old man was referred to our center because of low grade fever, vomiting, yellow sclera, and tenderness in the upper-right quadrant of his abdomen. Laboratory tests showed a white blood cell (WBC of 7100/µL, a platelet of 184,000/µL, an erythrocyte sedimentation rate (ESR of 4 mm/h, an alanine aminotransferase (ALT of 525 U/L, an aspartate aminotransferase AST of 142 U/L, a total bilirubin level of 4.23 mg/dL, and a direct bilirubin level of 3.16 mg/dL. Viral hepatitis markers, immunoglobuline M antibody to cytomegalovirus (anti-CMV IgM, Ebstein-Barr virus (EBV IgM, and immunologic markers of autoimmune hepatitis were negative. The patient was diagnosed with acute hepatitis. Alkaline phosphatase was in the normal range throughout the course of the disease. Because of the patient's occupation as a butcher and his history of eating semi-cooked sheep testes, serologic tests of brucellosis were conducted; the tests came out positive. We were concerned about the hepatotoxicity of standard regimens; therefore, we started treatment with streptomycin and ciprofloxacin regimens. Although liver enzyme had fallen and fever discontinued, the total and direct bilirubin concentrations in the patient's serum both increased in spite of using 2 weeks of the abovementioned drug regimen. The elevation of bilirubin could have been due to drug hepatotoxicity. Alternatively, a regimen containing ciprofloxacin may have not have been efficient enough and may have had effects on the direct bilirubin concentration. Fortunately, within 8 weeks, progressive recovery was noticed. Brucellosis should be considered in the differential diagnosis of fever and hepatitis for those who live in endemic areas, especially if his/her job was at high risk for acquiring brucellosis. We recommend taking a careful occupational and behavioral history for patients with acute hepatitis syndrome. We assumed that ciprofloxacin was not suitable for brucella hepatitis treatment and

  17. Identification of acute self-limited hepatitis B among patients presenting with hepatitis B virus-related acute hepatitis: a hospital-based epidemiological and clinical study.

    Science.gov (United States)

    Han, Y-N

    2009-01-01

    This study aimed to identify acute self-limited hepatitis B (ASL-HB) among patients presenting with hepatitis B virus (HBV)-related acute hepatitis. Data were available for 220 patients diagnosed with HBV-related acute hepatitis, of whom 164 had acute hepatitis B (AHB). Of these, 160 were confirmed as ASL-HB: three (1.9%) evolved to chronic hepatitis B and one (0.6%) developed fulminant hepatitis and died. Comparisons were also made between AHB and acute infections with hepatitis A (HA) and hepatitis E (HE) viruses. During the study period, the number of patients with AHB exceeded the sum of those with acute HA and acute HE infections. There was no distinct seasonal peak for AHB infection, whereas both acute HA and acute HE infections occurred more frequently in the spring. Clinical symptoms and physical signs were similar for all three types of hepatitis, but significant differences were seen in some biochemical parameters. In conclusion, this study suggests that symptomatic AHB is not rare in China but it seldom evolves to chronic hepatitis B.

  18. CT findings of hepatic abscess arising from perforated acute cholecystitis

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sang Hee; Lee, Kyoung Soo; Lee, Jin Seoung; Lee, Moon Gyu; Chung, Young Hwa; Lee, Young Sang; Lee, Sung Gyu; Auh, Yong Ho [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-01-01

    The purpose of this study was to report the CT findings of four patients with hepatic abscess secondary to perforated acute cholecystitis. We retrospectively reviewed the CT findings of four patients with surgically proven hepatic abscess secondary to perforated acute cholecystitis. CT findings were analysed with respect to the observation of the gallbladder, pericholecystic space, hepatic lesions, and peritoneal cavity. All patients underwent cholecystectomy, with drainage of the hepatic abscess. CT findings of hepatic abscess secondary to perforated acute cholecystitis were hypodense mass formation in the pericholecystic space(n=3), irreguarity and wall defect of Gallbladder(n=4), thickened Gallbladder wall(n=4), stone with debris(n=4), and local or diffuse infiltration of the pericholecystic area(n=3), omentum, and mesentery. CT was helpful in diagnosing the hepatic abscess secondary to perforated acute cholecystitis.

  19. A case of acute viral hepatitis interfering with acute fatty liver disease of pregnancy

    Directory of Open Access Journals (Sweden)

    Abdulkadir Turgut

    2013-03-01

    Full Text Available Acute hepatitis A is a rarely seen infection during pregnancy.In terms of clinical and laboratory findings, it can beinterfere with acute fatty liver disease which can be quitemortal during pregnancy. Since liver function tests are elevatedin both conditions, hepatitis A infection should alsobe kept in mind in differential diagnosis. We present a 30year-old pregnant woman with 35 weeks of gestation whopresented to our clinic with a suspection of acute fattyliver disease but finally diagnosed as acute hepatitis A infection.J Clin Exp Invest 2013; 4 (1: 123-125Key words: Hepatitis A, pregnancy, acute fatty liver disease

  20. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus

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    Amr Matoq

    2016-01-01

    Full Text Available Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection.

  1. Acute sporadic hepatitis E virus infection in southern China.

    Science.gov (United States)

    Tan, D; Im, S W; Yao, J L; Ng, M H

    1995-09-01

    The hepatitis E virus is responsible for epidemic and sporadic hepatitis in northwestern China, but its role as a cause of acute sporadic hepatitis in southern China has not been reported. We applied the most practical current methods for diagnosis of hepatitis E virus infection, IgM and IgG anti-HEV detection by enzyme linked immunosorbent assay, to investigate the prevalence of hepatitis E virus infection among acute sporadic hepatitis. Anti-HEV IgM was found in 1 of 26 (3.8%), 4 of 20 (20.0%), 4 of 19 (21.1%), and 51 of 142 (35.9%), with acute hepatitis A, B, C and non-ABC, respectively. Anti-HEV IgM was not detectable in healthy subjects, while IgG anti-HEV was found in 14 of 77 healthy subjects (18.2%) and was long-lasting. Ninety-one cases without any evidence of hepatitis A, B or C infections and anti-HEV IgM were tentatively classified as non-A, B, C, D, E (non-ABCDE) hepatitis. By comparison with non-ABCDE, cases with hepatitis E were more frequently icteric and exhibited higher alanine aminotransferase levels (92.2% vs. 45.1%, 770 iu/l vs 377 iu/l, respectively, p hepatitis E virus infections. However, 14 of 91 (15.4%) cases with non-ABCDE developed to chronicity (p Hepatitis E virus infection is sporadic as well as endemic in southern China. Only IgM anti-HEV but not IgG anti-HEV can be used as an appropriate marker of acute hepatitis E virus infection. Superinfection of hepatitis E virus with other types of hepatitis viruses is frequent in this area. While the disease was associated with more severe clinical manifestations, patients usually recovered completely.

  2. Astaxanthin pretreatment attenuates acetaminophen-induced liver injury in mice.

    Science.gov (United States)

    Zhang, Jingyao; Zhang, Simin; Bi, Jianbin; Gu, Jingxian; Deng, Yan; Liu, Chang

    2017-04-01

    Acetaminophen (APAP) is a conventional drug widely used in the clinic because of its antipyretic-analgesic effects. However, accidental or intentional APAP overdoses induce liver injury and even acute liver failure (ALF). Astaxanthin (ASX) is the strongest antioxidant in nature that shows preventive and therapeutic properties, such as ocular protection, anti-tumor, anti-diabetes, anti-inflammatory, and immunomodulatory effects. The aim of present study was to determine whether ASX pretreatment provides protection against APAP-induced liver failure. Male C57BL/6 mice were randomly divided into 7 groups, including control, oil, ASX (30mg/kg or 60mg/kg), APAP and APAP+ASX (30mg/kg or 60mg/kg) groups. Saline, olive oil and ASX were administered for 14days. The APAP and APAP+ASX groups were given a peritoneal injection of 700mg/kg or 300mg/kg APAP to determine the 5-day survival rate and for further observation, respectively. Blood and liver samples were collected to detect alanine transaminase (ALT), aspartate transaminase (AST), inflammation, oxidative stress and antioxidant systems, and to observe histopathologic changes and key proteins in the mitogen-activated protein kinase (MAPK) family. ASX pretreatment before APAP increased the 5-day survival rate in a dose-dependent manner and reduced the ALT, AST, hepatic necrosis, reactive oxygen species (ROS) generation, lipid peroxidation (LPO), oxidative stress and pro-inflammatory factors. ASX protected against APAP toxicity by inhibiting the depletion of glutathione (GSH) and superoxide dismutase (SOD). Administration of ASX did not change the expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and P38. However, phosphorylation of JNK, ERK and P38 was reduced, consistent with the level of tumor necrosis factor alpha (TNF-α) and TNF receptor-associated factor 2 (TRAF2). ASX provided protection for the liver against APAP hepatotoxicity by alleviating hepatocyte necrosis, blocking ROS

  3. Prevalence and severity of acute viral hepatitis and fulminant hepatitis during pregnancy: A prospective study from north india

    OpenAIRE

    Beniwal M; Kumar A; Kar P; Jilani N; Sharma J

    2003-01-01

    The present study aimed to find out the prevalence and severity of acute viral hepatitis and fulminant hepatitis during pregnancy in North India. The study was conducted on 97 consecutive pregnant patients in third trimester with acute viral hepatitis (AVH) or fulminant hepatic failure (FHF). The patients were evaluated on the basis of history, examination, liver function profile and serological markers for hepatitis A,B,C and E viruses. Hepatitis E virus (HEV) was the causative agent in 47.4...

  4. NNDSS - Table II. Hepatitis (viral, acute) A & B

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) A & B - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  5. Cytokine Signatures Discriminate Highly Frequent Acute Hepatitis a Virus and Hepatitis E Virus Coinfections from Monoinfections in Mexican Pediatric Patients.

    Science.gov (United States)

    Realpe-Quintero, Mauricio; Copado-Villagrana, Edgar Daniel; Trujillo-Ochoa, Jorge Luis; Alvarez, Angel Hilario; Panduro, Arturo; Fierro, Nora Alma

    2017-07-01

    The frequency of hepatitis A virus and hepatitis E virus infections and their cytokine profiles were analyzed in Mexican pediatric patients with acute hepatitis. A high frequency of coinfections was found. Significant overexpression of interleukin (IL)-4, IL-12, IL-13 and interferon-gamma during hepatitis A virus monoinfections and limited secretion of cytokines in hepatitis E virus infections were observed.

  6. [Clinical characteristics and incidence in acute non A-G hepatitis].

    Science.gov (United States)

    Yatsuhashi, H; Koga, M; Yano, M

    1999-06-01

    We investigated clinical characteristics and incidence of patients with acute non-A-G hepatitis, who were all registered in 17 Japanese National Hospitals. Seven hundreds thirty-one (24.0%) of 3052 patients with sporadic acute hepatitis and 73 (21.2%) of 344 patients with posttransfusion acute hepatitis were diagnosed as acute non-ABC hepatitis. Patients with acute non-ABC hepatitis were older (Mean +/- SD, 44 +/- 15 years) and male/female ratio was 0.70. Although mean levels of liver function abnormality was generally mild, 4(1.8%) of 250 patients with acute non-ABC hepatitis were died of fulminant hepatitis.

  7. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

    Directory of Open Access Journals (Sweden)

    Daniela Rodrigues

    2012-12-01

    Full Text Available CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7 hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. RESULTS: Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. CONCLUSION: These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.

  8. Pure Red Cell Aplasia Caused by Acute Hepatitis A

    OpenAIRE

    Lee, Tae Heon; Oh, Suk Joong; Hong, Soojung; Lee, Kyu Bek; Park, Hyosoon; Woo, Hee-Yeon

    2011-01-01

    Pure red cell aplasia is characterized as a normocytic anemia associated with reticulocytopenia and the absence of erythroblasts in the bone marrow. Pure red cell aplasia can be induced by various causes such as thymoma, connective tissue disease, viral infection, lymphoma, and adverse drug reactions. There have been only a few reports of pure red cell aplasia associated with acute viral hepatitis A. In Korea, no case of pure red cell aplasia caused by acute hepatitis A has yet been reported....

  9. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

    OpenAIRE

    Daniela Rodrigues; Themis Reverbel Da Silveira; Ursula Matte

    2012-01-01

    CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7) ...

  10. Acute Hepatitis E-Associated Acute Pancreatitis: A Single Center Experience and Literature Review.

    Science.gov (United States)

    Raj, Mithun; Kumar, Kundan; Ghoshal, Uday C; Saraswat, Vivek A; Aggarwal, Rakesh; Mohindra, Samir

    2015-11-01

    Because acute pancreatitis (AP) associated with acute hepatitis E is rarely reported, we present such a case series. Records of patients admitted with AP to our institution between May 2007 and December 2013 were reviewed. Diagnosis of AP and acute hepatitis E was based on high serum amylase and/or lipase (>3 times the upper normal limit) and abdominal imaging and presence of serum IgM antibodies against hepatitis E virus, respectively. Other causes of AP were excluded by appropriate evaluation. Of 790 patients with AP, 16 (2.1%; median [range] age, 25 [16-54] years; 15 males) had hepatitis E and no other cause of AP; coexistent hepatitis A and B were present in two and one of them, respectively. Acute pancreatitis began (median [range], 8 [0-35] days) after acute hepatitis and was mild in 10 and severe in 6. Complications included intra-abdominal collections (5), acute renal failure (4), and acute lung injury (2). Median (range) bilirubin, alanine aminotransferase, and prothrombin time were 9.8 (0.4-25) mg/dL, 822 (54-4009) IU/L, 14.6 (9.7-27.4) seconds, respectively. Acute liver failure occurred in 1 patient only. No patient needed surgical, endoscopic, or percutaneous intervention. Acute pancreatitis associated with hepatitis E is not uncommon and usually has good prognosis.

  11. Estimating Acute Viral Hepatitis Infections From Nationally Reported Cases

    Science.gov (United States)

    Liu, Stephen; Roberts, Henry; Jiles, Ruth B.; Holmberg, Scott D.

    2014-01-01

    Objectives. Because only a fraction of patients with acute viral hepatitis A, B, and C are reported through national surveillance to the Centers for Disease Control and Prevention, we estimated the true numbers. Methods. We applied a simple probabilistic model to estimate the fraction of patients with acute hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would have sought health care tests, and would have been reported to health officials in 2011. Results. For hepatitis A, the frequencies of symptoms (85%), care seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0 infections per reported case). For hepatitis B, the frequencies of symptoms (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5 infections per reported case). For hepatitis C, the frequency of symptoms among injection drug users (13%) and those infected otherwise (48%), proportion seeking care (88%), and percentage reported (53%) indicated 17 100 infections (12.3 infections per reported case). Conclusions. These adjustment factors will allow state and local health authorities to estimate acute hepatitis infections locally and plan prevention activities accordingly. PMID:24432918

  12. Acute Cholestatic Hepatitis Associated with Teucrium Polium

    Directory of Open Access Journals (Sweden)

    M Mohammadi

    2007-12-01

    Full Text Available Diabetes mellitus (DM is a metabolic disorder resulting from a defect in Insulin secretion, insulin action or both. Despite the fact that it has a worldwide high prevalence, morbidity and mortality, it is regarded as a non–curable but controllable disease. In addition to different synthetic drugs, plant remedies and dietary traditions play an effective role in treatment. Teucrium polium L. is one of the 300 species of the genus Teucrium and found mainly in the Mediterranean and Western lrano- Turanian sphere. lt is widely distributed in Jordan and Palestine. The leaves, 1-3 cm long, are sessile, oblong or linear, the stems are ending in shortly paniculate or corymbose inflorescences, and corolla is white or pale cream colored. This case describes a 74year old man with diabetes since 20 years. He was treated by glibenclamide 5mg/day. He stopped this drug and started daily consumption of tea containing the medicinal plant, teucrium polium. One month after initiation of this therapy, he developed an acute icteric hepatitis like illness. After 8 weeks, the patient recovered clinically and bilirubin, ALT and AST levels were normal.

  13. Dynamic epidemiology of acute viral hepatitis in Japan.

    Science.gov (United States)

    Yano, Koji; Tamada, Yoko; Yatsuhashi, Hiroshi; Komori, Atsumasa; Abiru, Seigo; Ito, Kiyoaki; Masaki, Naohiko; Mizokami, Masashi; Ishibashi, Hiromi

    2010-01-01

    The epidemiology of acute viral hepatitis (AVH) is dynamic and affected by many factors including hygiene, socioeconomic status and vaccination coverage. A total of 4,302 cases of AVH were sequentially enrolled in this nationwide study between 1980 and 2008. Of the cases of AVH, acute hepatitis A (AHA) accounted for 1,583 (36.8%), acute hepatitis B (AHB) for 1,197 (27.8%), acute hepatitis C (AHC) for 359 (8.3%), and non-A, non-B and non-C (non-ABC) for 1,163 (27.0%). Between 1980 and 1995, the proportions of AHA, AHB, AHC and non-ABC were approximately 40, 25, 10 and 25%; between 1996 and 2003, they were approximately 30, 30, 10 and 30%, and this shifted to approximately 10, 40, 10 and 40% in the last 5 years. The number of AHB caused by genotype A, which is not indigenous to Japan, was 6.0% between 1991 and 1996 but has been markedly increasing since 2000, to reach 52% in 2008. Autochthonous acute hepatitis E (AHE) accounted for 10-15% of non-ABC hepatitis after 2002. The etiology of AVH in Japan has been drastically changing. A marked increase of AHB genotype A and constant occurrence of autochthonous AHE require attention, and necessary measures should be taken. Copyright 2010 S. Karger AG, Basel.

  14. Effects of erdosteine on acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Kuvandik, Guven; Duru, Mehmet; Nacar, Ahmet; Yonden, Zafer; Helvaci, Rami; Koc, Ahmet; Kozlu, Tolunay; Kaya, Hasan; Sogüt, Sadik

    2008-07-01

    We investigated the effects of erdosteine on acetaminophen (APAP)-induced hepatotoxicity in rats. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), AST (aspartate aminotransferase), and ALT (alanine transaminase) activities, and malonyldialdehyde (MDA) and nitric oxide levels as oxidant/antioxidant biochemical parameters were investigated with light microscopic evaluation in adult female Wistar Albino rats. APAP administration produced a decrease in hepatic SOD, CAT, and GSH-Px activities, and coadministration of erdosteine (150 and 300 mg/kg) resulted in increases in the activities. MDA and NO levels increased in the APAP group, and erdosteine treatments prevented these increases. Significant elevations in serum AST and ALT levels were observed in the APAP group, and when erdosteine and APAP were coadministered, their serum levels were close to those in the control group. Light microscopic evaluation of livers showed that there were remarkable centrilobular (zone III) hepatic necrosis and mild to moderate sinusoidal congestion in the APAP group, whereas in the erdosteine group, cellular necrosis was minimal and the hepatocytes maintained a better morphology when compared to the APAP group. Erdosteine prevented APAP-induced liver injury and toxic side effects probably through the antioxidant and radical scavenging effects of erdosteine.

  15. [A study of 158 cases of acute delta hepatitis].

    Science.gov (United States)

    Castro, A; Buti, M; Esteban, R; Jardí, R; Allende, H; Roget, M; Rodríguez-Frías, F; Guardia, J

    1990-09-22

    We have prospectively studied 158 cases of acute hepatitis delta observed during the last 7 years in a general hospital. Among them 136 were male and 22 female. The mean age was 22.7 years with a range between 16 and 61 years. The epidemiologic factors were drug addiction by parenteral route in 145 cases (92%), sexual transmission in 5 (3%), post transfusional in 2 (1%) and unknown in 6 (4%). With respect to the delta type infection, 105 cases (66%) were coinfections with type B and delta, and 53 patients had a type delta superinfection (34%). The clinical course was a fulminant hepatitis in three cases (two cases of coinfection B and delta an one case of delta superinfection), and an acute benign hepatitis in 155 patients. The follow-up of 118 patients revealed that 96% of coinfections by type B and delta evolved to the chronicity showing findings of active chronic hepatitis or hepatic cirrhosis. It should be noted that in 4 cases of superinfection delta type (11%) the HBsAg was negative after several months of positivity. In these patients the level of transaminases normalized and the hepatic histology evidenced alterations of chronic active hepatitis (2 cases) and hepatic cirrhosis (2 cases) without identification of tissular delta antigen.

  16. Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

    Science.gov (United States)

    Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Buyankhuu, Osorjin; Baatarkhuu, Oidov; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2006-05-01

    One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia. Copyright 2006 Wiley-Liss, Inc.

  17. Acetaminophen-induced hepatotoxicity: Preventive effect of trans anethole.

    Science.gov (United States)

    da Rocha, Bruno Ambrósio; Ritter, Alessandra M Versuti; Ames, Franciele Queiroz; Gonçalves, Odinei Hess; Leimann, Fernanda Vitória; Bracht, Lívia; Natali, Maria Raquel Marçal; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Ap

    2017-02-01

    The hepatotoxicity induced by APAP is caused by the excessive production of N-acetyl-para-benzoquinone imine (NAPQI), which, when reacting with hepatic proteins proved to cause irreversible lesions. Associated with this process, an intense inflammatory process is also evidenced, characterized by the increased cell influx and production/release of inflammatory mediators. Trans anethole, an aromatic compounds has been showed anti-inflammatory efficacy by inhibit the cellular recruitment and synthesis/releases of many proinflammatory mediators such as prostaglandin (PGE2), cytokines (TNF, IL-1) and nitrico oxide (NO). The aim of this study is to investigate the effect of trans anethole on some inflammatory parameters that are involved in hepatotoxicity induced by high doses of acetaminophen. Our results demonstrate that treatment with AN at doses 125 and 250mg/kg once a day for seven days prevented the changes caused by the APAP overdose, showing less intensity in the histological changes (necrosis, size of hepatocyte area and inflammatory infiltration), and corroborating the findings of serum activities of transaminases and phosphatases and the activity of the enzyme myeloperoxidase. In addition, the treatment prevented the up-regulation of proinflammatory mediators such as NO, TNF, IL-1α, MIP-1α and MCP-1 and induced the up-regulation of anti-inflammatory cytokines (IL-4 and IL-10). Thus, our results demonstrate a possible protective effect of trans anethole on the hepatotoxicity induced by APAP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Experience with lamivudine treatment for severe acute hepatitis B

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    Verhaz Antonija

    2014-01-01

    Full Text Available Introduction. Experience with lamivudine treatment for acute severe hepatitis B is limited. Fulminant hepatitis develops in 1% of immunocompetent patients with acute hepatitis B. Objective. The aim of this study was to evaluate the efficacy of lamivudine in the treatment of severe acute hepatitis B (SAHB in immunocompetent adult patients. Methods. Between January 2006 and May 2013 at the Clinic for Infectious Diseases Banja Luka, 13 patients with SAHB were treated with lamivudine at a dose of 100 mg per day. All 13 patients fulfilled at least two of three default criteria: 1. hepatic encephalopathy; 2. total bilirubin greater than 210 μmol/L; and 3. severe coagulopathy (international normalized ratio - INR ≥1.5 or prothrombin time - PT <40%. The criteria were defined according to the experiences reported in the study of Schmilovitz-Weiss et al. ”Lamivudine treatment for severe acute hepatitis B“. Nine patients had a rapid rise in the total bilirubin and decrease of alanine aminotransferase level, which escalated risk for development of fulminant hepatitis. Results. Within 1-6 months, HBsAg was undetectable in 12 of 13 examined patients. Protective anti-HBsAg developed in 10 of them during 2-14 months. Two patients did not develop protective antibodies, but the result of the analysis of PCR HBV DNA was repeatedly negative. Corticosteroids were shortly used in two patients. One patient died four days after starting the therapy. Lamivudine treatment was well tolerated by all patients. Conclusion. Early treatment with lamivudine can reduce the risk of progression to fulminant hepatitis in patients with SAHB.

  19. Acute hepatitis B or exacerbation of chronic hepatitis B-that is the question

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. In countries with intermediate or high endemicity for HBV, exacerbations of chronic hepatitis B may be the first presentation of HBV infection. Some of these patients may be diagnosed mistakenly as having acute hepatitis B. Accurate diagnosis in these cases is very important for deciding whether to start treatment or not, because acute hepatitis B does not require therapy, while exacerbation of chronic hepatitis may benefit from it. Clinical and routine laboratory findings cannot help distinguishing between these two conditions. Therefore, several assays have been proposed for this purpose during the last few years. The presence of high levels of anti-HBe antibodies, HBsAg and HBV DNA are typical of chronic disease, whereas high titers of IgM anti-HBc, together with their high avidity index, characterize acute HBV infection. StarLing from the description of a patient with acute hepatitis B-who recently came to our observation-we critically review the currentlyavailable assays that may help distinguishing between the different conditions and lead to the optimal management of each patient.

  20. Hepatitis E in liver biopsies from patients with acute hepatitis of clinically unexplained origin.

    Directory of Open Access Journals (Sweden)

    Uta eDrebber

    2013-12-01

    Full Text Available Hepatitis E virus (HEV is a small RNA virus and the infectious agent of hepatitis E that occurs worldwide either as epidemics in Asia caused by genotype 1 and 2 or as sporadic disease in industrialized countries induced by genotype 3 and 4. The frequency might be underestimated in central Europe as a cause of acute hepatitis. Therefore, we analyzed on liver biopsies, if cases of acute hepatitis with clinically unknown or obscure diagnosis were actually caused by the infection with HEV.We included 221 liver biopsies retrieved from the files of the institute of pathology during the years 2000 till 2010 that were taken from patients with acute hepatitis of obscure or doubtful diagnosis. From all biopsies RNA was extracted, prepared, and subjected to RT-PCR with specific primers. Amplified RNA was detected in 7 patients, sequenced and the genotype 3 could be determined in four of the seven of positive specimens from 221 samples. Histopathology of the biopsies revealed a classic acute hepatitis with cholestatic features and in some cases confluent necrosis in zone 3. Histology in a cohort of matched patients was less severe and showed more eosinophils. The analysis of the immune response by subtyping of liver infiltrating lymphocytes showed circumstantial evidence of adaptive immune reaction with CD 8 positive CTLs being the dominant lymphocyte population.In conclusion, in doubtful cases of acute hepatitis of unknown origine hepatitis E virus infection should be considered as etiology in central Europe. We demonstrate for the first time that the diagnosis can be made in paraffin-embedded liver biopsies reliably when no serum is available and also the genotype can be determined. The analysis of the immune response by subtyping of liver infiltrating lymphocytes indicates an adaptive mechanism suggesting in analogy with HAV, HBV and HCV that the virus itself is not cytopathic but liver damage is due to immune reaction.

  1. Profile of acute infectious markers in sporadic hepatitis E.

    Directory of Open Access Journals (Sweden)

    Shoujie Huang

    Full Text Available Laboratory diagnosis of acute infection of hepatitis E virus (HEV is commonly based on the detection of HEV RNA, IgM and/or rising IgG levels. However, the profile of these markers when the patients present have not been well determined. To clarify the extent of misdiagnosed sporadic hepatitis E in the initial laboratory detection, serial sera of 271 sporadic acute hepatitis cases were collected, detected and the dynamics of each acute marker during the illness course were analyzed. 91 confirmed cases of hepatitis E were identified based on the presentation of HEV RNA, IgM or at least 4 fold rising of IgG levels. 21 (23.1% hepatitis E cases were false negative for the viral RNA and 40 (44.0% for rising IgG, because occurrence of these markers were confined to acute phase of infection and viremia had already subsided and antibody level peaked when these patients presented. IgM was detected in 82 (90.1% cases. It is the most prevalent of the three markers, because the antibody persisted until early convalescence. Nine cases negative for IgM were positive for rising IgG and one was also positive for the viral RNA; all of these nine cases showed high avid IgG in their acute phase sera, which indicated re-infection. In summary, it is not practicable to determine the true occurrence of sporadic hepatitis E. Nevertheless, it could be closely approximated by approach using a combination of all three acute markers.

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

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

  4. Acetaminophen Induced Hepatotoxicity in Wistar Rats--A Proteomic Approach.

    Science.gov (United States)

    Ilavenil, Soundharrajan; Al-Dhabi, Naif Abdullah; Srigopalram, Srisesharam; Ock Kim, Young; Agastian, Paul; Baru, Rajasekhar; Choi, Ki Choon; Valan Arasu, Mariadhas

    2016-01-28

    Understanding the mechanism of chemical toxicity, which is essential for cross-species and dose extrapolations, is a major challenge for toxicologists. Standard mechanistic studies in animals for examining the toxic and pathological changes associated with the chemical exposure have often been limited to the single end point or pathways. Toxicoproteomics represents a potential aid to the toxicologist to understand the multiple pathways involved in the mechanism of toxicity and also determine the biomarkers that are possible to predictive the toxicological response. We performed an acute toxicity study in Wistar rats with the prototype liver toxin; the acetaminophen (APAP) effects on protein profiles in the liver and its correlation with the plasma biochemical markers for liver injury were analyzed. Three separate groups--control, nontoxic (150 mg/kg) and toxic dose (1500 mg/kg) of APAP--were studied. The proteins extracted from the liver were separated by 2-DE and analyzed by MALDI-TOF. The differential proteins in the gels were analyzed by BIORAD's PDQuest software and identified by feeding the peptide mass fingerprint data to various public domain programs like Mascot and MS-Fit. The identified proteins in toxicity-induced rats were classified based on their putative protein functions, which are oxidative stress (31%), immunity (14%), neurological related (12%) and transporter proteins (2%), whereas in non-toxic dose-induced rats they were oxidative stress (9%), immunity (6%), neurological (14%) and transporter proteins (9%). It is evident that the percentages of oxidative stress and immunity-related proteins were up-regulated in toxicity-induced rats as compared with nontoxic and control rats. Some of the liver drug metabolizing and detoxifying enzymes were depleted under toxic conditions compared with non-toxic rats. Several other proteins were identified as a first step in developing an in-house rodent liver toxicoproteomics database.

  5. Acetaminophen Induced Hepatotoxicity in Wistar Rats—A Proteomic Approach

    Directory of Open Access Journals (Sweden)

    Soundharrajan Ilavenil

    2016-01-01

    Full Text Available Understanding the mechanism of chemical toxicity, which is essential for cross-species and dose extrapolations, is a major challenge for toxicologists. Standard mechanistic studies in animals for examining the toxic and pathological changes associated with the chemical exposure have often been limited to the single end point or pathways. Toxicoproteomics represents a potential aid to the toxicologist to understand the multiple pathways involved in the mechanism of toxicity and also determine the biomarkers that are possible to predictive the toxicological response. We performed an acute toxicity study in Wistar rats with the prototype liver toxin; the acetaminophen (APAP effects on protein profiles in the liver and its correlation with the plasma biochemical markers for liver injury were analyzed. Three separate groups—control, nontoxic (150 mg/kg and toxic dose (1500 mg/kg of APAP—were studied. The proteins extracted from the liver were separated by 2-DE and analyzed by MALDI-TOF. The differential proteins in the gels were analyzed by BIORAD’s PDQuest software and identified by feeding the peptide mass fingerprint data to various public domain programs like Mascot and MS-Fit. The identified proteins in toxicity-induced rats were classified based on their putative protein functions, which are oxidative stress (31%, immunity (14%, neurological related (12% and transporter proteins (2%, whereas in non-toxic dose-induced rats they were  oxidative stress (9%, immunity (6%, neurological (14% and transporter proteins (9%. It is evident that the percentages of oxidative stress and immunity-related proteins were up-regulated in toxicity-induced rats as compared with nontoxic and control rats. Some of the liver drug metabolizing and detoxifying enzymes were depleted under toxic conditions compared with non-toxic rats. Several other proteins were identified as a first step in developing an in-house rodent liver toxicoproteomics database.

  6. Acute pancreatitis associated with acute viral hepatitis A (HAV) - a case report.

    Science.gov (United States)

    Arafat, S M; Azad, A K; Basher, A; Ananna, M A; Islam, M S; Abdullah, S; Abdullah, A M; Islam, M A

    2013-01-01

    In this case report, a young woman had acute viral hepatitis (HAV) and acute pancreatitis together. She was admitted to our hospital with fever, jaundice and abdominal pain. Hepatic and pancreatic enzymes were elevated. Her serum alanine aminotransferase (ALT) level was high. An initial abdominal ultrasound was per-formed at hospital and revealed features of acute viral hepatitis. Spiral computed imaging revealed imaging features of an acute stage of pancreatitis and gallbladder wall thickness. HAV infection was diagnosed by the detection of immunoglobulin M (IgM) against HAV in the serum. She was closely monitored and treated conservatively. On 10th day of hospital admission she was discharge after an uneventful recovery. In the current literature HAV infections have rarely been reported as a cause of acute pancreatitis.

  7. [Hepatitis non-A, non-B: epidemiological significance in acute viral hepatitis and chronic active hepatitis of hepatological consultation].

    Science.gov (United States)

    Jmelnitzky, A C; Basualdo, J A; Belloni, P O; Ponce de León, H H; García, C; Curciarello, J

    1987-01-01

    157 acute viral hepatitis and 60 chronic active ones have been analyzed focusing on NANB etiology. HAV was implicated in 36.3% of the hole acute viral hepatitis sample, HBV in 29.3%, and HNANBV was presumed as etiology in 31.2%, 5 patients (3.2%) had acute infection by HAV, on previous one by HBV, except for Epstein-Barr virus, no other test for viruses were determined (CMV, HSV, etc.). Male/female ratio was 1.4:1, 1.9:1, and 1.4:1 for HAV, HBV and HNANBV acute hepatitis respectively; HAV was the main etiology in the 0-9 age group (72.2%) although it only represents 11.5% of the sample; small occurrence of HAV hepatitis were found in patients over 40 (8.8%); HBV was clearly prevalent in patients over 50 (65.2%); the highest concentration of NANB etiology was found between 20-39 years old, but it was represented in all age-groups. Out of 49 NANB acute hepatitis, 12.2% had related transfusional antecedents, 12.2% belonged to health care worker group, and 4.1% had a close family NANB hepatitis contact; 71.5% had no reported antecedent. Viral source was presumably implicated in 75.0% of chronic active hepatitis, 25.0% attributable to HNANBV. Results seem not feasible to transfer to general population due to the facts that most patients were of specialized consult, and pediatric assistance is unusual to the authors practice.

  8. Effect of IL-10 mRNA expression in acetaminophen-induced hepatotoxicity%白细胞介素-10mRNA表达在对乙酰氨基酚所致肝损害中的作用

    Institute of Scientific and Technical Information of China (English)

    田丰; 解莹; 张亚杰

    2012-01-01

    Objective To investigate the role of interleukin-10( IL-10 ) in acetaminophen-induced hepatotoxic-ity. Methods To establish the model of acetaminophen-induced hepatotoxicity in SD rats. The levels of serum ALT of AAP group and control group were measured by radioimmunoassay. Hepatic tissue samples were taken to evaluate pathological changes by HE staining and the IL-10 mRNA expression was detected by RT-PCR. Results Compared to control group, serum ALT( nKat/L )were progressively increased after acetaminophen administration( P < 0. 01 )in different time periods; Liver pathological damage were progressively exacerbated; The expression of IL-10 mRNA in liver tissue increased significantly( P <0. 01 ),and reached a peak at 12 h. Conclusion IL-10 has a strong inhibitory effect on pro-inflammatory cytokine expression, which may play a protective role in acetaminophen-induced hepatotoxicity.%目的 探讨白细胞介素-10(IL-10)在AAP肝损害中的作用.方法 应用对乙酰氨基酚(AAP)建立SD大鼠肝损害模型;AAP组和对照组分别测定血清ALT水平,HE染色观察肝脏病理变化,RT-PCR方法检测大鼠肝组织中IL-10 mRNA的表达.结果 AAP组和对照组相比,各时间点血清ALT水平均显著升高(P<0.01);肝脏病理损伤进行性加剧;肝组织IL-10 mRNA表达显著升高(P<0.01),于12 h达高峰.结论 IL-10可能具有抑制促炎因子表达作用,在AAP引起的肝损害中可能起到肝脏保护作用.

  9. Free radical scavenging activity of Berberine in acetaminophen induced liver injury

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    Suhail Ahmed Almani

    2017-01-01

    Full Text Available Objective: Evaluation of free radical scavenging activity of Berberine (BBR in acetaminophen (AAP induced liver injury. Study design: Experimental study Place and Duration: Animal house, Isra University Hyderabad from October 2015 to March 2016. Methodology: A sample of 80 male Wistar rats was selected according to inclusion and exclusion criteria and was divided into a control and three experimental groups. Acetaminophen, N-acetyl cysteine (NAC and BBR were administered in standard doses. Blood samples were collected by cardiac puncture after 18 hours of post experiment period. Liver function test, anti oxidant enzymes and malondialdehyde (MDA were detected by ELISA assay kit (Fortress Diagnostics. The data was analyzed on Statistix 10.0 software (USA at 95% CI (P≤ 0.05. Results: The BBR showed anti oxidant and anti peroxidant activity against acetaminophen induced liver injury. BBR treated animals showed increased serum and tissue SOD, GPX, CAT, and GSSH with a reduction in tissue MDA (p=0.0001. Liver injury ameliorating effect of BBR was superior to N-acetyl cysteine. Conclusion: The present study suggests Berberine protects against acetaminophen-induced liver injury by its free radical scavenging activity.

  10. Current knowledge and future perspectives on acute hepatitis C infection

    NARCIS (Netherlands)

    Hullegie, S. J.; Arends, J. E.; Rijnders, B. J A; Irving, W. L.; Salmon, D.; Prins, M.; Wensing, A. M.; Klenerman, P.; Leblebicioglu, H.; Boesecke, C.; Rockstroh, J. K.; Hoepelman, A. I M

    2015-01-01

    Acute hepatitis C virus (HCV) infections are frequently seen worldwide in certain risk groups, with an annual incidence rate varying between 0.08% and 66%. Although this incidence is substantial, a delayed diagnosis during chronic infection is most often made in the absence of clinical symptoms in

  11. Sonographic changes of liver and gallbladder in acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    Ebrahimi Daryani N

    2001-07-01

    Full Text Available Hepatomegaly, decrease in the liver paranchymal echo and increase in the gallbladder wall thickness has been shown in acute viral hepatitis. The present study was done to determine sonographic changes in acute viral hepatitis. We performed liver and bile ducts sonography and specific tests on 42 patients (mean age: 31.5 and 61% male with acute viral hepatitis. Gallbladder wall thickness was seen in 45.2% and hepatomegaly in 33.3% of patients and liver paranchymal echo was decreased in 19.3%. Age, sex, type of hepatitis, cholecystitis like symptoms, aspartate aminotransfrase, alanine aminotransfrase, alkaline phosphatase and bilirubin did not significantly corralate with these changes. Only raised prothrombin time was strongly correlated to the thickening of the gallbladder and decrease in the liver paranchymal echo and cholesistic like symptoms we can postulate that thickening of the gallbladder and decrease in the liver paranchymal echo is not dependent on the severity and speed of the paranchymal necrosis (as considered with ALT and AST but they depend on the liver function disturbance (as considered with PT because the thickening of the gall bladder is present in 45% of the patients and 10% of the normal population have gallbladder stones, one should not perform the diagnosis of acute cholecystitis, only on the basis of sonographic report without attention to the clinical and laboratory data.

  12. [Hepatic retransplant and acute Budd Chiari syndrome. Case report].

    Science.gov (United States)

    Savio-López, Andrés M; Lara-Molina, Evelin E; Soliva-Domínguez, Ramón; Capo-Jorge, José A; Gala-López, Boris; González-Castillo, Fernando

    2005-01-01

    Hepatic retransplant constitutes 10-20% of all orthotopic hepatic transplants. The piggy-back technique was used in hepatectomy with conservation of the retrohepatic vena cava. A side-to-side cavo-cavostomy technique is described in the case of hepatic congestion or acute Budd Chiari syndrome post-transplant. This is an extremely serious condition and can result in death. We present the first case of hepatic retransplant performed in Hospital Hermanos Ameijeiras in a patient who received who received his first transplant due to non-resectable hepatocarcinoma and who required retransplant due to acute rejection and graft dysfunction. During retransplant, the Belghiti side-to-side anastomosis technique was used to resolve the acute Budd Chiari syndrome that presented itself. Post-surgical evolution at 18 months was satisfactory without evidence of complications of the graft. Acute Budd Chiari syndrome post-transplant can satisfactorily be resolved with the Belghiti technique, although it is preferable to take prophylactic measures to avoid it.

  13. Liver function tests in acute hepatitis in children

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    Shweta

    2016-08-01

    Conclusions: This study helps us to analyze the incidence of HBsAg positive cases presenting with clinical features of acute hepatitis and degree of alteration of liver functions would help the physician in better management of the cases. [Int J Res Med Sci 2016; 4(8.000: 3184-3187

  14. [Consistency analysis on acute hepatitis B inpatients reported by hepatitis B surveillance pilot spots in six provinces of China].

    Science.gov (United States)

    Miao, N; Zhang, G M; Wang, F Z; Zheng, H; Sun, X J; Ma, X J; Cui, F Q

    2017-02-10

    Objective: To understand the characteristics of acute hepatitis B inpatients reported by the hepatitis B surveillance pilot points and to estimate the consistency between the diagnosed and reported types of hepatitis B by the clinicians involved. Methods: Data related to acute hepatitis B was from the NNDRS and the characteristics of acute hepatitis B were classified by querying Hospital Information System. We recorded the results based on clinical diagnosis and analyzed the consistency between the reported and diagnosed types that the clinicians made, on hepatitis B. Results: A total of 179 patients were included in this study with all of them as acute hepatitis B reported through NNDRS in 2015-2016. In terms of the durations of disease, among the 179 cases who were HBsAg positive, 32.40% (58/179) of them exceeding 6 months, 2.79% (5/179) within 6 months and 64.80% (116/179) tested the first time or never. Among the 179 cases who claimed having the history of hepatitis, 33.52% (60/179) of them identified as having hepatitis B, 1.12% (2/179) were hepatitis A, C or E, 41.34% (74/179) did not have the signs on hepatitis, while the rest 24.02% (43/179) did not know the situation. Only 79.89% (143/179) of the patients showed the symptoms or signs of hepatitis, but the rest 20.11% (36/179) did not. Among the 179 reported acute hepatitis patients, 67 of them were diagnosed as acute hepatitis B while 112 cases were as non-acute hepatitis B. The consistent rate of acute hepatitis B was 37.43% (67/179). Among the 112 cases that were diagnosed as non-acute hepatitis B, proportions of chronic hepatitis B and cirrhosis were 49.11%(55/112) and 16.07%(18/112) respectively. Conclusion: Consistency between the reported type of acute hepatitis B inpatients and the types diagnosed by clinicians was poor. Our results suggested that clinicians should make the accurate diagnosis at first place and then report to the Network in accordance with the clinical diagnosis classification

  15. The transcriptional change of mitochondrial genome in mice models for acetaminophen-induced acute liver injury and failure%对乙酰氨基酚诱导的急性肝损伤和肝衰竭模型中线粒体基因组转录改变

    Institute of Scientific and Technical Information of China (English)

    明雅南; 李春敏; 张静怡; 刘晓琳; 茅益民

    2016-01-01

    Objective To explore the relationship between transcription level of mitochondrial DNA (mtDNA ) and disease progression in the mice models of acetaminophen (APAP)‐induced acute liver injury (AILI) and acute liver failure (ALF) ,and to find the relative new biomarkers for outcome .Methods Ninety mice were randomly divided into three groups ,including control group ,AILI group (300 mg/kg) and ALF group (750 mg/kg) .After fasting 16 h ,all mice were intraperitoneally injected with same volume of saline or different doses of APAP .At different time points of 0 ,1 ,3 ,6 and 12 h , 6 mice randomly selected from each group were sacrificed for blood and liver , respectively . Plasma alanine aminotransferase (ALT ) ,aspartate aminotransferase (AST ) and reactive oxygen (ROS ) levels were detected ,and liver total RNA was extracted for RT‐PCR to detect changes in transcription of mitochondrial genome .Results Compared with the control group ,ALT and AST levels in AILI and ALF group were significantly increased .In AILI group ,ALT peaked at 6‐12 h (5000‐10000 IU/L) ,and ALT exceeded 10000 IU/L at 12 h in ALF group ,which showed significantly difference (P<0 .05) .Microbubbles steatosis in three zones was observed in both AILI and ALF groups ,and massive hepatic necrosis (MHN) were found merely in ALF group .In 1 h after APAP injection ,ROS in ALF group was about 2 .5 times as much as that in AILI group ,which significantly increased at all time points in both group .Contrasting with control and ALIF groups ,COX1 transcriptional level in AILI group increased significantly at 6 h .In AILI and ALF group ,CYTB ,COX2 and ATP8 reduced significantly at 3 h (P<0 .05) ,COX1 ,ND1 ,ND5 and ATP8 significantly decreased at 6 h (P<0 .05) ,and transcription level of other subunits of NADH significantly decreased at 12 h (P<0 .05) comparing with those in control group .Furthermore ,ATP6 at 6h in ALF group was obviously lower than that in AILI and control group (P<0 .05) .At 12 h

  16. Butachlor-induced acute toxic hepatitis.

    Science.gov (United States)

    Daryani, Nasser Ebrahimi; Hosseini, Parviz; Bashashati, Mohammad; Haidarali, Mona; Sayyah, Alireza

    2007-01-01

    Butachlor is a highly effective herbicidal substance widely used by farmers. We report a 60-year-old man with exfoliative dermatitis, jaundice, increase in liver enzymes and eosinophilia one day after accidental dermal exposure to butachlor toxin. The diagnostic workup showed no other cause and liver histology was consistent with substance-induced toxic hepatitis. Within two weeks of conservative therapy, his liver function tests returned to normal.

  17. Acute Hepatic Failure in a Dog after Xylitol Ingestion.

    Science.gov (United States)

    Schmid, Renee D; Hovda, Lynn R

    2016-06-01

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

  18. Dengue hemorrhagic fever and acute hepatitis: a case report

    Directory of Open Access Journals (Sweden)

    Maria Paula Gomes Mourão

    Full Text Available Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  19. Dengue hemorrhagic fever and acute hepatitis: a case report

    Directory of Open Access Journals (Sweden)

    Maria Paula Gomes Mourão

    2004-12-01

    Full Text Available Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  20. Acute exacerbation of autoimmune hepatitis induced by Twinrix

    Institute of Scientific and Technical Information of China (English)

    Antal Csepregi; Gerhard Treiber; Christoph R(o)cken; Peter Malfertheiner

    2005-01-01

    We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix(○R). In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid,and led to complete normalization of the pathological liver function tests. We believe that Twinrix(○R) led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

  1. Hepatitis E virus as a Cause of Acute Hepatitis in The Netherlands.

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    Aletta T R Tholen

    Full Text Available Recent studies indicate that 27% of Dutch blood donors have evidence of past infection with HEV. However, the low number of diagnosed HEV infections indicates either an asymptomatic course or under diagnosis.We investigated whether HEV is a cause of acute hepatitis in Dutch patients and which diagnostic modality (serology or PCR should be used for optimal detection.Serum samples were retrospectively selected from non-severely immuno-compromised patients from a university hospital population, suspected of having an infectious hepatitis. Criteria were: elevated alanine aminotransferase (ALT> 34 U/l and request for antibody testing for CMV, EBV or Hepatitis A (HAV.All samples were tested for HEV using ELISA and PCR. Ninety patients/sera were tested, of which 22% were HEV IgG positive. Only one serum was IgM positive. HEV PCR was positive in two patients: one patient was both HEV IgM and IgG positive, the other patient was only IgG positive. Both HEV RNA positive samples belonged to genotype 3. Evidence of recent infection with CMV, EBV and HAV was found in 13%, 10% and 3% respectively.Although our study is limited by small numbers, we conclude that HEV is a cause of acute hepatitis in hospital associated patients in The Netherlands. Moreover, in our study population the prevalence of acute HAV (3% was almost similar to acute HEV (2%. We propose to incorporate HEV testing in panels for acute infectious hepatitis. Negative results obtained for HEV IgM in a HEV PCR positive patient, indicates that antibody testing alone may not be sufficient and argues for PCR as a primary diagnostic tool in hospital associated patients. The high percentage of HEV IgG seropositivity confirms earlier epidemiological studies.

  2. Rat liver arginase system under acetaminophen-induced toxic injury and protein deprivation

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    H. P. Kopylchuk

    2017-04-01

    Full Text Available Arginase activity and L-arginine content in both cytosolic and mitochondrial fractions of rat liver cells under the conditions of toxic injury on the background of protein deprivation was studied. The most significant reduction of arginase activity in liver cells and depletion of L-arginine pool was found in rats with toxic acetaminophen-induced liver injury maintained on the ration balanced by all nutrients as well as in protein deficiency rats. It was concluded that reduction of the arginase activity in the cytosolic fraction of rat liver cells, combined with simultaneous decrease of L-arginine content, may be considered as one of the mechanisms of ornithine cycle disturbance. The decline of activity of mitochondrial isoform of arginase II, for certain, is related with activation of NO-synthase system.

  3. Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage

    Science.gov (United States)

    Schreiter, Thomas; Sowa, Jan-Peter; Schlattjan, Martin; Treckmann, Jürgen; Paul, Andreas; Strucksberg, Karl-Heinz; Baba, Hideo A.; Odenthal, Margarete; Gieseler, Robert K.; Gerken, Guido; Arteel, Gavin E.; Canbay, Ali

    2016-01-01

    Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period. Three liver sections incubated with low-dose acetaminophen revealed strong damage, with ICG half-lives significantly higher than in non-treated livers. In addition, the release of microRNA-122 was significantly higher in acetaminophen-treated than in non-treated livers. Thus, this model allows for investigation of hepatotoxicity in human liver tissue upon applying drug concentrations relevant in patients. PMID:27550092

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

    Science.gov (United States)

    Lee, Guan-Huei

    2015-10-01

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

  5. Severe Aplastic Anemia following Parvovirus B19-Associated Acute Hepatitis

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    Masanori Furukawa

    2017-01-01

    Full Text Available Human parvovirus (HPV B19 is linked to a variety of clinical manifestations, such as erythema infectiosum, nonimmune hydrops fetalis, and transient aplastic anemia. Although a few cases have shown HPVB19 infection as a possible causative agent for hepatitis-associated aplastic anemia (HAAA in immunocompetent patients, most reported cases of HAAA following transient hepatitis did not have delayed remission. Here we report a rare case of severe aplastic anemia following acute hepatitis with prolonged jaundice due to HPVB19 infection in a previously healthy young male. Clinical laboratory examination assessed marked liver injury and jaundice as well as peripheral pancytopenia, and bone marrow biopsy revealed severe hypoplasia and fatty replacement. HPVB19 infection was diagnosed by enzyme immunoassay with high titer of anti-HPVB19 immunoglobulin M antibodies. Immunosuppressive therapy was initiated 2 months after the onset of acute hepatitis when liver injury and jaundice were improved. Cyclosporine provided partial remission after 2 months of medication without bone marrow transplantation. Our case suggests that HPVB19 should be considered as a hepatotropic virus and a cause of acquired aplastic anemia, including HAAA.

  6. Acute viral hepatitis in Hong Kong: a study of recent incidences.

    Science.gov (United States)

    Chau, T N; Lai, S T; Lai, J Y; Yuen, H

    1997-09-01

    Acute hepatitis patients admitted to a referral centre from January 1995 through December 1995 were studied to determine the seroprevalence of the hepatitis viruses and related risk factors. Of the 434 patients with acute viral hepatitis, the episodes due to hepatitis A, B, C, D, and non-A, non-B, non-C, (non-ABC) were 214 (49.3%), 163 (37.6%), 7 (1.6%), 0 (0%), and 50 (11.5%), respectively. Acute hepatitis A and non-ABC hepatitis commonly occur in late spring and early summer and are probably related to the intake of shellfish and travel to endemic areas. Approximately 60% of cases of symptomatic hepatitis B infection were acute exacerbations of chronic infection. Sexual exposure was the single most important risk factor for acute hepatitis B infection. The rarity of acute hepatitis C and D might be related to the low rate of intravenous drug use in our locality. Hepatitis E virus probably contributed significantly to the cases of non-ABC hepatitis. Further studies are needed to establish the importance of various causative agents of acute hepatitis in Hong Kong.

  7. Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: a hospital based study.

    Science.gov (United States)

    Jain, P; Prakash, S; Gupta, S; Singh, K P; Shrivastava, S; Singh, D D; Singh, J; Jain, A

    2013-01-01

    Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Fisher's exact test was used and a P hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.

  8. Clinical epidemiology of acute hepatitis C in South America.

    Science.gov (United States)

    Dirchwolf, Melisa; Marciano, Sebastián; Mauro, Ezequiel; Ruf, Andrés Eduardo; Rezzonico, Lucrecia; Anders, Margarita; Chiodi, Daniela; Petta, Néstor Gill; Borzi, Silvia; Tanno, Federico; Ridruejo, Ezequiel; Barreyro, Fernando; Shulman, Carolina; Plaza, Pablo; Carbonetti, Rodolfo; Tadey, Luciana; Schroder, Teresa; Fainboim, Hugo

    2017-02-01

    There is scarce data pertaining to acute hepatitis C (aHC) infection in South America. We aimed to describe clinical characteristics and evolution of aHC in a South American cohort. A retrospective survey was conducted at 13 hepatology units. All patients ≥16 years old with aHC diagnosis were included. Demographic, clinical and outcome information were registered in a standardized ad hoc questionnaire. Sixty-four patients were included. The majority were middle-aged (median age: 46 years) and female (65.6%); most of them were symptomatic at diagnosis (79.6%). HCV-1 was the most prevalent genotype (69.2%). Five patients had liver failure: three cases of severe acute hepatitis, one case of fulminant hepatitis and one case of acute-on-chronic liver failure. Nosocomial exposure was the most prevalent risk factor. Evolution was assessed in 46 patients. In the untreated cohort, spontaneous resolution occurred in 45.8% and was associated with higher values of AST/ALT and with the absence of intermittent HCV RNA viremia (P = 0.01, 0.05, and 0.01, respectively). In the treated cohort, sustained virological response was associated with nosocomial transmission and early treatment initiation (P = 0.04 each). The prevalence of nosocomial transmission in this South-American cohort of aHC stresses the importance of following universal precautions to prevent HCV infection. J. Med. Virol. 89:276-283, 2017. © 2016 Wiley Periodicals, Inc.

  9. Immune thrombocytopenic purpura as sole manifestation in a case of acute hepatitis A.

    Science.gov (United States)

    Tanir, Gönül; Aydemir, Cumhur; Tuygun, Nilden; Kaya, Ozge; Yarali, Neşe

    2005-12-01

    Acute hepatitis due to hepatitis A virus is usually a benign selflimiting disease during childhood. Although many viral infections such as hepatitis B virus, Parvovirus, and Epstein-Barr virus are associated with extrahepatic autoimmune phenomena, such manifestations are rare in patients with acute hepatitis A infection. Immune thrombocytopenia is a benign, self-limiting disease in children, responding well to treatment and generally associated with viral infections. Immune thrombocytopenic purpura is rarely reported as a manifestation of acute hepatitis A. We report a five-year-old boy with immune thrombocytopenic purpura as the sole manifestation of anicteric acute hepatitis A infection. Acute hepatitis A should be included in the differential diagnosis of immune thrombocytopenic purpura.

  10. Acute hepatitis A induction of precursor B-cell acute lymphoblastic leukemia: a causal relationship?

    Science.gov (United States)

    Senadhi, V; Emuron, D; Gupta, R

    2010-09-01

    Precursor B-cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the United States and occurs most frequently in childhood, but can also occur in adults with a median age of 39 years. It is more commonly seen in males and in Caucasians. We present a case of a 51-year-old Caucasian female with the development of precursor B-cell acute lymphoblastic leukemia after suffering acute hepatitis A 4 weeks prior to her diagnosis. She presented with malaise for a month without spontaneous bruising/bleeding, infections, or B-symptoms, such as fevers, night sweats, or unintentional weight loss. Nonspecific viral transformation of bone marrow has been discussed in the literature, but we specifically describe hepatitis A-induced adult-onset precursor B-cell acute lymphoblastic leukemia, which is the first reported case in the literature.

  11. Protection against acetaminophen-induced liver injury by allopurinol is dependent on aldehyde oxidase-mediated liver preconditioning

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C. David; McGill, Mitchell R.; Lebofsky, Margitta; Bajt, Mary Lynn; Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu

    2014-02-01

    Acetaminophen (APAP) overdose causes severe and occasionally fatal liver injury. Numerous drugs that attenuate APAP toxicity have been described. However these compounds frequently protect by cytochrome P450 inhibition, thereby preventing the initiating step of toxicity. We have previously shown that pretreatment with allopurinol can effectively protect against APAP toxicity, but the mechanism remains unclear. In the current study, C3HeB/FeJ mice were administered allopurinol 18 h or 1 h prior to an APAP overdose. Administration of allopurinol 18 h prior to APAP overdose resulted in an 88% reduction in liver injury (serum ALT) 6 h after APAP; however, 1 h pretreatment offered no protection. APAP-cysteine adducts and glutathione depletion kinetics were similar with or without allopurinol pretreatment. The phosphorylation and mitochondrial translocation of c-jun-N-terminal-kinase (JNK) have been implicated in the progression of APAP toxicity. In our study we showed equivalent early JNK activation (2 h) however late JNK activation (6 h) was attenuated in allopurinol treated mice, which suggests that later JNK activation is more critical for the toxicity. Additional mice were administered oxypurinol (primary metabolite of allopurinol) 18 h or 1 h pre-APAP, but neither treatment protected. This finding implicated an aldehyde oxidase (AO)-mediated metabolism of allopurinol, so mice were treated with hydralazine to inhibit AO prior to allopurinol/APAP administration, which eliminated the protective effects of allopurinol. We evaluated potential targets of AO-mediated preconditioning and found increased hepatic metallothionein 18 h post-allopurinol. These data show metabolism of allopurinol occurring independent of P450 isoenzymes preconditions the liver and renders the animal less susceptible to an APAP overdose. - Highlights: • 18 h allopurinol pretreatment protects against acetaminophen-induced liver injury. • 1 h allopurinol pretreatment does not protect from APAP

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

    Directory of Open Access Journals (Sweden)

    J Kee Ho

    2005-01-01

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

  13. Hepatitis C virus acquisition among Egyptians: analysis of a 10-year surveillance of acute hepatitis C.

    Science.gov (United States)

    Mohsen, Amira; Bernier, Adeline; LeFouler, Lenaig; Delarocque-Astagneau, Elisabeth; El-Daly, Mai; El-Kafrawy, Sherif; El-Mango, Salwa; Abdel-Hamid, Mohamed; Gadallah, Mohsen; Esmat, Gamal; Mohamed, Mostafa K; Fontanet, Arnaud

    2015-01-01

    To identify current risk factors for hepatitis C virus (HCV) acquisition among Egyptians. Patients with acute HCV were identified through a surveillance system of acute hepatitis in four fever hospitals in Egypt between 2002 and 2012. Case-control analysis was conducted, cases being incident acute symptomatic HCV and controls being acute hepatitis A identified at the same hospitals. The questionnaire covered iatrogenic, community and household exposures to HCV in the 1-6 months prior to onset of symptoms. Multivariate models were built to identify risk factors associated with HCV acquisition among non-drug users and drug users separately. Among non-drug users, hospital admission was independently associated with acute HCV infection (OR = 4.2, 95% CI = 1.7-10.5). Several iatrogenic procedures, for example admission in a surgery unit, sutures, IV injections and IV infusions, highly correlated with hospital admission, were also associated with acute HCV infection and could have been used in the final model instead of hospital admission. Among drug users, identified risk factors were multiple sexual relations (OR = 4.0, 95% CI = 1.1-14.7), intravenous drug use (OR = 3.9, 95% CI = 1.2-13.0) and shaving at the barbershops (OR = 8.7, 95% CI = 2.4-31.4). Illiteracy and marriage were significant risk factors in both groups. Invasive medical procedures are still a major risk for acquiring new HCV infections in Egypt, as is illicit drug use in spreading HCV infection. © 2014 John Wiley & Sons Ltd.

  14. A homosexual japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis

    OpenAIRE

    Sakaguchi, Kohsaku; KOBASHI, HARUHIKO; Takaki,Akinobu; Kato, Jun; Nawa,Toru; Tatsukawa, Masashi; ISHIKAWA, SHIN; Iwasaki, Yoshiaki; Miyake,Yasuhiro; Shiratori, Yasushi

    2007-01-01

    We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past ...

  15. Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Gerald C Kimbi; Anna Kramvis; Michael C Kew

    2005-01-01

    AIM: To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation.METHODS: DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced.RESULTS: HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nudeotide deletion. The right virus/host junction was situated at nucleotide 1774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged.The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time.CONCLUSION: Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis.

  16. [Two cases of acute hepatitis associated with Q fever].

    Science.gov (United States)

    Yeşilyurt, Murat; Kılıç, Selçuk; Gürsoy, Bensu; Celebi, Bekir; Yerer, Mehmet

    2012-07-01

    Q fever which is caused by Coxiella burnetii, is a worldwide zoonosis. Many species of wild and domestic mammals, birds, and arthropods, are reservoirs of C.burnetii in nature, however farm animals are the most frequent sources of human infection. The most frequent way of transmission is by inhalation of contaminated aerosols. The clinical presentation of Q fever is polymorphic and nonspecific. Q fever may present as acute or chronic disease. In acute cases, the most common clinical syndromes are selflimited febrile illness, granulomatous hepatitis, and pneumonia, but it can also be asymptomatic. Fever with hepatitis associated with Q fever has rarely been described in the literature. Herein we report two cases of C.burnetii hepatitis presented with jaundice. In May 2011, two male cases, who inhabited in Malkara village of Tekirdag province (located at Trace region of Turkey), were admitted to the hospital with the complaints of persistent high grade fever, chills and sweats, icterus, disseminated myalgia and headache. Physical examination revealed fever, icterus and the patient appeared to be mildly ill but had no localizing signs of infection. Radiological findings of the patients were in normal limits. Laboratory findings revealed leukocytosis, increased hepatic and cholestatic enzyme levels, and moderate hyperbilirubinemia- mainly direct bilirubin, whereas serum C-reactive protein and erythrocyte sedimentation rate were found normal. Blood and urine cultures of the patients yielded no bacterial growth. Serological markers for acute viral hepatitis, citomegalovirus and Epstein-Barr virus infections, brucellosis, salmonellosis, toxoplasmosis and leptospirosis were found negative. Acute Q fever diagnosis of the cases were based on the positive results obtained by C.burnetii Phase II IgM and IgG ELISA (Vircell SL, Spain) test, and the serological diagnosis were confirmed by Phase I and II immunofluorescence (Vircell SL, Spain) method. Both cases were treated with

  17. Hepatoprotective activity of Tribulus terrestris extract against acetaminophen-induced toxicity in a freshwater fish (Oreochromis mossambicus).

    Science.gov (United States)

    Kavitha, P; Ramesh, R; Bupesh, G; Stalin, A; Subramanian, P

    2011-12-01

    The potential protective role of Tribulus terrestris in acetaminophen-induced hepatotoxicity in Oreochromis mossambicus was investigated. The effect of oral exposure of acetaminophen (500 mg/kg) in O. mossambicus at 24-h duration was evaluated. The plant extract (250 mg/kg) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity. It was judged from the tissue-damaging level and antioxidant levels in liver, gill, muscle and kidney tissues. Further acetaminophen impact induced a significant rise in the tissue-damaging level, and the antioxidant level was discernible from the enzyme activity modulations such as glutamate oxaloacetic transaminase, glutamate pyruvic transaminase, alkaline phosphatase, acid phosphatase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, lipid peroxidase and reduced glutathione. The levels of all these enzymes have significantly (p terrestris extract (250 kg/mg). Histopathological changes of liver, gill and muscle samples were compared with respective controls. The results of the present study specify the hepatoprotective and antioxidant properties of T. terrestris against acetaminophen-induced toxicity in freshwater fish, O. mossambicus.

  18. Targeted metabolomic study indicating glycyrrhizin’s protection against acetaminophen-induced liver damage through reversing fatty acid metabolism.

    Science.gov (United States)

    Yu, Jian; Jiang, Yang-Shen; Jiang, Yuan; Peng, Yan-Fang; Sun, Zhuang; Dai, Xiao-Nan; Cao, Qiu-Ting; Sun, Ying-Ming; Han, Jing-Chun; Gao, Ya-Jie

    2014-06-01

    The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen-induced liver toxicity. Seven-day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2- to 3-month-old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen-induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra-fast liquid chromatography coupled to triple time-of-flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin-treated, acetaminophen-treated, and glycyrrhizin+acetaminophen-treated groups. Long-chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long-chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen-induced liver damage through reversing fatty acid metabolism.

  19. ERK Signaling Pathway Plays a Key Role in Baicalin Protection Against Acetaminophen-Induced Liver Injury.

    Science.gov (United States)

    Liao, Chia-Chih; Day, Yuan-Ji; Lee, Hung-Chen; Liou, Jiin-Tarng; Chou, An-Hsun; Liu, Fu-Chao

    2017-01-01

    Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15-60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.

  20. Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A

    Directory of Open Access Journals (Sweden)

    Y. Wan

    2014-08-01

    Full Text Available Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg was injected iv into mice 30 min after concanavalin A (Con A challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST. Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg. Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and transforming growth factor beta (TGF-β pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR. NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.

  1. Effect of a bioflavonoid dietary supplement on acetaminophen-induced oxidative injury to feline erythrocytes.

    Science.gov (United States)

    Allison, R W; Lassen, E D; Burkhard, M J; Lappin, M R

    2000-10-15

    To determine the effect of a commercial bioflavonoid antioxidant on acetaminophen-induced oxidative injury to feline erythrocytes. Randomized controlled study. 45 healthy age-matched cats. Cats were assigned to 3 experimental groups. Groups 1 and 3 received a bioflavonoid antioxidant (10 mg/d) orally for 2 weeks. Groups 2 and 3 received an oxidative challenge with acetaminophen (90 mg/kg [41 mg/lb] of body weight, PO) on day 7. Packed cell volume, percentage of erythrocytes with Heinz bodies, blood methemoglobin concentration, and blood reduced and oxidized glutathione concentrations were determined at various times during the 2-week study period. Adverse effects were not associated with bioflavonoid antioxidant administration alone. Acetaminophen administration resulted in a significant increase in methemoglobin concentration in groups 2 and 3; differences were not detected between these groups. Heinz body concentrations in groups 2 and 3 increased after acetaminophen administration; however, the increase in cats that received the antioxidant was significantly less than in group-2 cats. Total blood glutathione concentrations did not change significantly in groups 2 and 3 after acetaminophen administration; however, ratio of reduced to oxidized glutathione concentration increased significantly after administration in group-2 cats, compared with group-3 cats. Oral administration of bioflavonoid antioxidants to cats at risk for oxidative stress may have a beneficial effect on their ability to resist oxidative injury to erythrocytes.

  2. Piperine, an active ingredient of black pepper attenuates acetaminophen-induced hepatotoxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Evan Prince Sabina; Annie Deborah Harris Souriyan; Deborah Jackline; Mahaboob Khan Rasool

    2010-01-01

    Objective: To explore the hepatoprotective and antioxidant effects of piperine against acetaminophen-induced hepatotoxicity in mice. Methods: In mice, hepatotoxicity was induced by a single dose of acetaminophen (900 mg/kg b.w. i.p.). Piperine (25 mg/kg b.w. i.p.) and standard drug silymarin (25 mg/kg b.w. i.p.) were given to mice, 30 min after the single injection of acetaminophen. After 4 h, the mice were decapitated. Activities of liver marker enzymes [(aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP)] and inflammatory mediator tumour necrosis factor-alpha (TNF-α) were estimated in serum, while lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase and glutathione) were determined in liver homogenate of control and experimental mice. Results: Acetaminophen induction (900 mg/kg b.w. i.p.) significantly increased the levels of liver marker enzymes, TNF-α, and lipid peroxidation, and caused the depletion of antioxidant status. Piperine and silymarin treatment to acetaminophen challenged mice resulted in decreased liver marker enzymes activity, TNF-α and lipid peroxidation levels with increase in antioxidant status. Conclusions: The results clearly demonstrate that piperine shows promising hepatoprotective effect as comparable to standard drug silymarin.

  3. Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage.

    Science.gov (United States)

    Lin, S C; Chung, T C; Lin, C C; Ueng, T H; Lin, Y H; Lin, S Y; Wang, L Y

    2000-01-01

    The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.

  4. Risk factors of acute hepatic failure during antituberculosis treatment: two cases and literature review

    NARCIS (Netherlands)

    Smink, F.; van Hoek, B.; Ringers, J.; van Altena, R.; Arend, S.M.

    2006-01-01

    Hepatotoxicity is a well-known side effect of antituberculosis treatment (ATT). If not recognised in time, drug-induced hepatitis can develop, which may rapidly progress to acute liver failure. We describe two patients with acute hepatic failure caused by ATT, whose pretreatment liver function had b

  5. Risk factors of acute hepatic failure during antituberculosis treatment : two cases and literature review

    NARCIS (Netherlands)

    Smink, F.; van Hoek, B.; Ringers, J.; van Altena, R.; Arend, S. M.

    2006-01-01

    Hepatotoxicity is a well-known side effect of antituberculosis treatment (ATT). If not recognised in time, drug-induced hepatitis can develop, which may rapidly progress to acute liver failure. We describe two patients with acute hepatic failure caused by ATT, whose pretreatment liver function had b

  6. Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans

    DEFF Research Database (Denmark)

    Jürgens, Gesche; Christensen, Hanne Rolighed; Brøsen, Kim;

    2002-01-01

    Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.......Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes....

  7. Acute hepatitis with observed increased blood phenytoin level:a case study

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2014-01-01

    Acute hepatitis is a common problem in medical practice.This problem can be fatal if there is no proper management.For management, the investigation for the cause is necessary.In the case report, the authors present an interesting male case presenting with unexplained acute hepatitis.The routine laboratory investigation cannot reveal the cause of hepatitis.The additional toxicological drug test can reveal the unexplained increased level of phenytoin.

  8. Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

    Directory of Open Access Journals (Sweden)

    Wei-Lun Tsai

    2015-11-01

    Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

  9. [Acute hepatitis in a patient with adult onset Still disease].

    Science.gov (United States)

    Gallo, M; Calvanese, A; Oscuro, F; Gallo, A; Caso, P; Annibale, E; Farinato, N

    1997-04-01

    Liver abnormalities in the course of Adult Onset Still's Disease (AOSD), both in form of hepatomegaly and elevation of hepatic enzymes, have been reported in up to three-quarts of the affected patients. These abnormalities may reflect disease activity or may be induced by drugs. Only in a few of this patients a liver biopsy was performed. However liver histology has shown, generally, non specific abnormalities or even normal pictures. We have recently observed a 47-year-old woman with a febrile illness started five months before, who after pertinent investigation was diagnosed as AOSD (according to criteria of Yamaguchi et al.). Apart from laboratory findings characteristic of an inflammatory disease, in absence of drug therapies the biochemical data showed raised levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and aminoglutamil transferase. Serological tests for either viral hepatitis viruses (HAV, HBV, HCV) or other viruses were negative. Ultrasonographic examination of gallbladder and bile ducts did not find gallstones or other abnormalities. A liver biopsy was performed, which histopathologic examination showed moderate fatty methamorphosis with focal areas of hepatocellular swelling with minimal necrosis, mild Kuppfer cell hyperplasia, portal and sinusoidal infiltrates of mononuclear cells. This picture consisted with the diagnosis of an acute unspecific reactive hepatitis.

  10. Prevalence of Hepatitis A virus (HAV) and Hepatitis E virus (HEV) in the patients presenting with acute viral hepatitis.

    Science.gov (United States)

    Joon, A; Rao, P; Shenoy, S M; Baliga, S

    2015-02-01

    Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are both enterically transmitted, resulting in acute viral hepatitis (AVH) in developing countries. They pose major health problems in our country. This study was done to determine prevalence of HAV and HEV in patients presenting with AVH and the co-infection of HAV and HEV in these patients. A cross-sectional study of 2-years duration was conducted in the Department of Microbiology, KMC, Mangalore. A non-random sampling of 958 patients presenting with AVH was considered in the study. On the basis of history, serum samples were analysed for IgM anti-HAV and IgM anti-HEV for the detection of HAV and HEV, respectively using commercially available ELISA kits. Data collected was analysed by using Statistical Package for the Social Sciences (SPSS) version 11.5. The seroprevalence of HAV- and HEV-positive patients were 19.31% and 10.54%, respectively. The seroprevalence of both HAV and HEV in patients with acute viral hepatitis was 11.5%. The prevalence of HAV and HEV among males (68% and 31%) was higher than in females (31% and 20%) and was predominantly seen among young adults. These infections were predominantly seen during end of monsoons and beginning of winter. Though the prevalence of HAV is much higher than that of HEV, co-infection rate of 11.5% mandates the screening for HEV which will be of immense importance in pregnant women and improving levels of personal hygiene among higher socio-economic population. These data will be essential for planning of future vaccination strategies and for better sanitation programme in this part of the country.

  11. Hepatic artery pseudoaneurysm caused by acute idiopathic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yeon Hwa Yu; Joo Hyun Sohn; Tae Yeob Kim; Jae Yoon Jeong; Dong Soo Han; Yong Cheol Jeon; Min Young Kim

    2012-01-01

    Hepatic artery pseudoaneurysm (HAP) is a very rare disease but in cases of complication,there is a very high mortality.The most common cause of HAP is iatrogenic trauma such as liver biopsy,transhepatic biliary drainage,cholecystectomy and hepatectomy.HAP may also occur with complications such as infections or inflammation associated with septic emboli.HAP has been reported rarely in patients with acute pancreatitis.As far as we are aware,there is no report of a case caused by acute idiopathic pancreatitis,particularly.We report a case of HAP caused by acute idiopathic pancreatitis which developed in a 61-year-old woman.The woman initially presented with acute pancreatitis due to unknown cause.After conservative management,her symptoms seemed to have improved.But eight days after admission,abdominal pain abruptly became worse again.Abdominal computed tomography (CT) was rechecked and it detected a new HAP that was not seen in a previous abdominal CT.Endoscopic retrograde cholangiopancreatography (ERCP) was performed because of a suspicion of hemobilia as a cause of aggravated abdominal pain.ERCP confirmed hemobilia by observing fresh blood clots at the opening of the ampulla and several filling defects in the distal common bile duct on cholangiogram.Without any particular treatment such as embolization or surgical ligation,HAP thrombosed spontaneously.Three months after discharge,abdominal CT demonstrated that HAP in the left lateral segment had disappeared.

  12. Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury.

    Science.gov (United States)

    Naguib, Yahya M; Azmy, Rania M; Samaka, Rehab M; Salem, Mohamed F

    2014-12-15

    Acetaminophen (APAP)-induced toxicity is a predominant cause of acute hepatic and renal failure. In both humans and rodents toxicity begins with a reactive metabolite that binds to proteins. This leads to mitochondrial dysfunction and nuclear DNA fragmentation resulting in necrotic cell death. Pleurotus ostreatus (an edible oyster mushroom) is well recognized as a flavourful food, as well as a medicinal supplement. In the present study, we evaluated the role of Pleurotus ostreatus in the protection against APAP-induced hepato-renal toxicity. We also explored the mechanism by which Pleurotus ostreatus exerts its effects. Ninety adult male Swiss albino mice were divided into three groups (30 mice/group). Mice were offered normal diet (control and APAP groups), or diet supplemented with 10% Pleurotus ostreatus (APAP + Pleurotus ostreatus) for 10 days. Mice were either treated with vehicle (control group, single intra-peritoneal injection.), or APAP (APAP and APAP + Pleurotus ostreatus groups, single intra-peritoneal injection, 500 mg/kg), 24 hours after the last meal. APAP increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) glutamate dehydrogenase (GDH), creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), and hepatic and renal malondialdehyde (MDA) content. APAP decreased hepatic and renal glutathione (GSH) content, as well as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Supplementation with Pleurotus ostreatus significantly reduced APAP-induced elevated levels of ALT, AST, GDH, creatinine, BUN, KIM-1and MDA, while GSH level, and GSH-Px and SOD activities were significantly increased. Our findings were further validated by histopathology; treatment with Pleurotus ostreatus significantly decreased APAP-induced cell necrosis in liver and kidney tissues. We report here that the antioxidant effect of Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative

  13. Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice

    Science.gov (United States)

    Silva-Filho, Saulo Euclides; Cardia, Gabriel Fernando Esteves; Cremer, Edivaldo; Bersani-Amado, Ciomar Aparecida

    2017-01-01

    High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP. PMID:28717379

  14. Acute hepatitis induced by an Aloe vera preparation: A case report

    Institute of Scientific and Technical Information of China (English)

    Christian Rabe; Annemarie Musch; Peter Schirmacher; Wolfgang Kruis; Robert Hoffmann

    2005-01-01

    AIM: Aloe vera, plant extracts of Aloe barbadensis miller,is widely used in phytomedicine. The first case of acute hepatitis due to this compound was described.METHODS: Description of a clinical case.RESULTS: Hepatitis in a 57-year old female could be linked to the ingestion of Aloe barbadensis miller compounds. The patient's hepatitis resolved completely after discontinuing this medication.CONCLUSION: The case emphasizes the importance of considering phytopharmaceutical over-the-counter drugs as causative agents of hepatitis.

  15. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005226 Characteristics of peripheral blood T lymphocyte subsets in hepatitis B patients. FAN Zhen-ping(范振平),et al. Center Bio Ther, Instit Infect Dis, 302 Hosp Chin PLA, Beijing 100039. World Chin J Digestol, 2005;13(2): 194-197. Objective: To characterize the T-lymphocyte subsets in peripheral blood of patients with acute and chronic hepatitis B, and to explore their relations with the disease state. Methods: Peripheral blood

  16. Acute seronegative hepatitis C manifesting itself as adult giant cell hepatitis--a case report and review of literature.

    Science.gov (United States)

    Kryczka, Wiesław; Walewska-Zielecka, Bozena; Dutkiewicz, Ewa

    2003-08-01

    Adult giant cell hepatitis (AGCH) is a rare event and only about 100 cases have been reported within the last 20 years. The AGCH has been observed in association with viral infection, drug reactions or autoimmune disorders but in many cases its etiology remains unclear. AGCH manifests clinically as severe form of hepatitis histologically characterized by diffuse giant cell transformation of hepatocytes. We report the case of a 39-yr-old man with acute community-acquired hepatitis without previous pathology of the liver. Laboratory data revealed slight hypergammaglobulinemia and high titer of anti-smooth-muscle antibody with negative serology of hepatotropic viruses and absence of other known causes of hepatitis. Preliminary diagnosis of autoimmune hepatitis was established, additionally confirmed by excellent clinical and biochemical improvement during corticosteroid treatment. A liver biopsy showed the typical findings of panlobular syncytial giant cell hepatitis and positive HCV-RNA both in serum and liver. The above verified the diagnosis of acute type C hepatitis manifested histologically as adult giant cell hepatitis. After three months of treatment we withdrew corticosteroids as spontaneous clearance of HCV occurred and the lack of autoantibodies in serum as well as significant improvement of liver histology was ascertained. Within 30 months of the follow-up we have not observed biochemical and immunological abnormalities and control liver biopsy has shown no signs of hepatitis.

  17. Propolis reverses acetaminophen induced acute hepatorenal alterations: a biochemical and histopathological approach.

    Science.gov (United States)

    Nirala, Satendra Kumar; Bhadauria, Monika

    2008-04-01

    The present study has been conducted to evaluate the curative effect of propolis extract, a honey bee-hive product, against acetaminophen (APAP) induced oxidative stress and dysfunction in liver and kidney. Animals were challenged with APAP (2 g/kg, p.o.) followed by treatment of propolis extract (100 and 200 mg/kg, p.o.) once only after 24 h. Release of transaminases, alkaline phosphatase, lactate dehydrogenase, and serum bilirubin were increased, whereas hemoglobin and blood sugar were decreased after APAP administration. Antioxidant status in both the liver and kidney tissues were estimated by determining the glutathione, malondialdehyde content and activities of the CYP enzymes, which showed significant alterations after APAP intoxication. In addition, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase, and major cell contents (total protein, glycogen and cholesterol) were also altered due to APAP poisoning. Propolis extract successfully reversed the alterations of these biochemical variables at higher dose. Improvements in hepatorenal histoarchitecture were also consistent with biochemical observations. The results indicated that ethanolic extract of propolis has ability to reverse APAP-induced hepatorenal biochemical and histopathological alterations probably by increasing the antioxidative defense activities due to various phenolic compounds present in it.

  18. Molecular characterization of hepatitis E virus in patients with acute hepatitis in Venezuela.

    Science.gov (United States)

    García, Cristina Gutiérrez; Sánchez, Doneyla; Villalba, Maria Caridad Montalvo; Pujol, Flor Helene; de Los Ángeles Rodríguez Lay, Licel; Pinto, Belquis; Chacón, Elsa Patricia; Guzmán, Maria Guadalupe

    2012-07-01

    Hepatitis E virus (HEV) causes a common infection in developing countries. HEV infection occurs as outbreaks, as sporadic clinical cases and as large epidemics in endemic areas. The objective of this study was to determine the presence of HEV infection in patients with clinical suspicion of hepatitis A virus (HAV) infection, referred to the Instituto Nacional de Higiene "Rafael Rangel" in Venezuela. Seventy-four sera were tested for anti-HAV and anti-HEV IgM antibodies. HEV-RNA was amplified from anti-HEV IgM positive sera using nested reverse transcription polymerase chain reaction for ORF1 (RNA dependent RNA polymerase region) and the amplicons sequenced for phylogenetic analysis. The frequency of anti-HEV IgM was 22/74 (30%) in the samples tested. Dual infection with HAV and HEV was found in 31% (12/39) of anti-HAV IgM positive patients. Viremia was detected in 3/22 (14%) of sera positive for anti-HEV IgM. Two HEV strains were classified as genotype 1 and one as genotype 3, which were closely related to Yam 67 (north of India) and US1 isolates from the USA, respectively. These findings suggest that HEV is an important cause of acute viral hepatitis in Venezuela as a single infection or co-infection with HAV, with high morbidity in children and young adults suggesting that this infection is endemic in Venezuela. Copyright © 2012 Wiley Periodicals, Inc.

  19. Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A.

    Science.gov (United States)

    Hussain, Zahid; Husain, Syed A; Almajhdi, Fahad N; Kar, Premashis

    2011-05-23

    Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.

  20. Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A

    Science.gov (United States)

    2011-01-01

    Background Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. Objective In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. Methods Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. Results Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity. PMID:21605420

  1. Effect of gomisin A in an immunologically-induced acute hepatic failure model.

    Science.gov (United States)

    Mizoguchi, Y; Shin, T; Kobayashi, K; Morisawa, S

    1991-02-01

    Guinea pigs were sensitized with trinitrophenylated liver macromolecular protein fraction (TNP-LP1) prepared by using sodium trinitrobenzenesulfonate of strong immunogenicity as the hapten and LP1 as the carrier protein. The administration of trinitrophenylated hepatocytes and lipopolysaccharide to these TNP-LP1-sensitized guinea pigs through the mesenteric vein 2 weeks later resulted in the induction of acute hepatic failure accompanied by massive hepatic cell necrosis in almost all of the guinea pigs. Using this experimental model, the effect of Gomisin A on the induction of immunological acute hepatic failure was examined. As a result, the administration of gomisin A remarkably improved the survival rate and serum transaminase levels of the immunologically-induced acute hepatic failure guinea pigs. Gomisin A also improved the histological changes of the liver in these guinea pigs. These results suggested that gomisin A is effective for the improvement of immunologically-induced acute hepatic failure in our experimental model.

  2. Treatment with lamivudine and entecavir in severe acute hepatitis B

    Directory of Open Access Journals (Sweden)

    A Streinu-Cercel

    2016-01-01

    Full Text Available Background: Severe acute hepatitis B (SAHB is an insufficiently described clinical entity, with relatively scarce data on anti-viral therapy available in field literature. Methods: We performed an open-label study to evaluate specific anti-viral therapy in SAHB in Bucharest, Romania, during 2005-2009. Patients were allocated to two treatment groups and one control group: Group 1 - lamivudine 100 mg/day, Group 2 - entecavir 0.5 mg/day and Group 3 - standard of care, without anti-viral therapy. The primary endpoint was hepatitis B surface antigen (HBsAg to hepatitis B surface antibody (anti-HBs seroconversion by 24 weeks. Additional analyses included assessment of HBsAg clearance and hepatitis B e antigen (HBeAg to hepatitis B e antibody (anti-HBe seroconversion. Results: In Group 1, 7/69 patients (10.14%, P = 0.032 reached HBsAg/Ab seroconversion by 24 weeks, compared with 9/21 (42.85%, P = 0.053 in Group 2 and 25/110 (22.72% in Group 3. HBsAg clearance by 24 weeks: 16/69 patients (23.18%, P = 0.027 in Group 1, 11/21 (52.38%, P = 0.256 in Group 2 and 43/110 (39.09% in Group 3. HBeAg/Ab seroconversion: 46/61 (75.40%, P = 0.399 in Group 1, 9/19 (47.36%, P = 0.001 in Group 2 and 74/100 (74.00% in Group 3. Conclusion: Anti-viral therapy can be considered for managing selected cases of SAHB. Biochemical as well as virological parameters need to orient the choice of the anti-viral agent. Lamivudine displayed a greater decrease in viral load compared to controls, but it was associated with lower levels of HBsAg to anti-HBs seroconversion. Patients treated with entecavir showed a better response in terms of HBs seroconversion by 24 weeks.

  3. Prevalence of hepatitis viruses in patients with acute hepatitis and characterization of the detected genotype 4 hepatitis E virus sequences in Mongolia.

    Science.gov (United States)

    Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Okamoto, Hiroaki

    2016-02-01

    Hepatitis E is considered to be a worldwide public health problem. Although the prevalence of hepatitis E virus (HEV) antibodies in healthy individuals is noted to be 11%, no patients with acute hepatitis E have previously been identified in Mongolia. Three hundred two consecutive patients (183 males and 119 females; median age of 22.0 [Interquartile range: 18.3-25.0] years) who were clinically diagnosed with sporadic acute hepatitis during 2012-2013 in Ulaanbaatar, Mongolia, were studied. By serological and/or molecular approaches, 77 (25.5%), 93 (30.8%), 19 (6.3%), 48 (15.9%), and 12 (4.0%) of the patients were diagnosed with acute hepatitis of types A, B, C, D (superinfection of hepatitis delta virus on a background of chronic hepatitis B virus infection) and E, respectively, while the cause of hepatitis was unknown in the remaining 53 patients (17.5%). The 12 hepatitis E patients had no history of travel abroad in the 3 months before the onset of disease, and lived separately in fixed or movable houses with water supplied via pipe, tank or well, denying transmission from a common water supply. The 12 HEV isolates obtained from the patients showed high nucleotide identities of 99.7-100%, and a representative HEV isolate, MNE13-227, was closest to the Chinese isolates of genotype 4, with the highest identity of 97.3% in the 304-nt ORF2 sequence and 92.1% over the entire genome. The present study revealed the occurrence of autochthonous acute hepatitis E in Mongolia, caused by a monophyletic genotype 4 HEV strain.

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Formononetin protects against acetaminophen-induced hepatotoxicity through enhanced NRF2 activity.

    Science.gov (United States)

    Jin, Fen; Wan, Chunpeng; Li, Weifang; Yao, Liangliang; Zhao, Hongqian; Zou, Yuan; Peng, Dewei; Huang, Weifeng

    2017-01-01

    To examine the effects of formononetin (FMN) on Acetaminophen (APAP)-induced liver injury in vitro and in vivo. Human non-tumor hepatic cells LO2 were pretreated with either vehicle or FMN (20, 40 μM), for 6 h, followed by incubation with or without APAP (10 mM) for 24 h. In an in vivo assay, male BALB/c mice were randomly divided into four groups: (1) control group; (2) APAP group; (3) APAP + FMN (50 mg/Kg); (4) APAP + FMN (100 mg/Kg). The mice in the control and APAP groups were pre-treated with vehicle; the other two groups were pretreated daily with FMN (50, 100 mg/Kg) orally for 7 consecutive days. After the final treatment, acute liver injury was induced in all groups, except the control group, by intraperitoneal (i.p.) injection of 300 mg/Kg APAP. In LO2 cells, APAP exposure decreased the cell viability and glutathione (GSH) content, which were both greatly restored by FMN pretreatment. Overdose of APAP increased hepatic malondialdehyde (MDA) content, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity in experimental mice. Supplementation with 100 mg/Kg FMN significantly reduced APAP-induced elevated levels of MDA (1.97 ± 0.27 vs 0.55 ± 0.14 nmol/mg protein, p < 0.001), ALT (955.80 ± 209.40 vs 46.90 ± 20.40 IU/L, p < 0.001) and AST (1533.80 ± 244.80 vs 56.70 ± 28.80 IU/L, p < 0.001), and hepatic GSH level (5.54 ± 0.93 vs 8.91 ± 1.11 μmol/mg protein, p < 0.001) was significantly increased. These results were further validated by histopathology and TdT-mediated biotin-dUTP nick-endlabeling (TUNEL) staining, pretreatment with 100 mg/Kg FMN significant decreased APAP-induced hepatocellular damage and cell apoptosis (36.55 ± 3.82 vs 2.58 ± 1.80%, p < 0.001). Concomitantly, FMN stimulated the expression of Nrf2 and antioxidant gene expression in the presence of APAP. These data provide an experimental basis for the use of FMN in the treatment of patients with APAP-induced hepatotoxicity.

  6. Formononetin protects against acetaminophen-induced hepatotoxicity through enhanced NRF2 activity

    Science.gov (United States)

    Li, Weifang; Yao, Liangliang; Zhao, Hongqian; Zou, Yuan; Peng, Dewei; Huang, Weifeng

    2017-01-01

    To examine the effects of formononetin (FMN) on Acetaminophen (APAP)-induced liver injury in vitro and in vivo. Human non-tumor hepatic cells LO2 were pretreated with either vehicle or FMN (20, 40 μM), for 6 h, followed by incubation with or without APAP (10 mM) for 24 h. In an in vivo assay, male BALB/c mice were randomly divided into four groups: (1) control group; (2) APAP group; (3) APAP + FMN (50 mg/Kg); (4) APAP + FMN (100 mg/Kg). The mice in the control and APAP groups were pre-treated with vehicle; the other two groups were pretreated daily with FMN (50, 100 mg/Kg) orally for 7 consecutive days. After the final treatment, acute liver injury was induced in all groups, except the control group, by intraperitoneal (i.p.) injection of 300 mg/Kg APAP. In LO2 cells, APAP exposure decreased the cell viability and glutathione (GSH) content, which were both greatly restored by FMN pretreatment. Overdose of APAP increased hepatic malondialdehyde (MDA) content, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity in experimental mice. Supplementation with 100 mg/Kg FMN significantly reduced APAP-induced elevated levels of MDA (1.97 ± 0.27 vs 0.55 ± 0.14 nmol/mg protein, p < 0.001), ALT (955.80 ± 209.40 vs 46.90 ± 20.40 IU/L, p < 0.001) and AST (1533.80 ± 244.80 vs 56.70 ± 28.80 IU/L, p < 0.001), and hepatic GSH level (5.54 ± 0.93 vs 8.91 ± 1.11 μmol/mg protein, p < 0.001) was significantly increased. These results were further validated by histopathology and TdT-mediated biotin-dUTP nick-endlabeling (TUNEL) staining, pretreatment with 100 mg/Kg FMN significant decreased APAP-induced hepatocellular damage and cell apoptosis (36.55 ± 3.82 vs 2.58 ± 1.80%, p < 0.001). Concomitantly, FMN stimulated the expression of Nrf2 and antioxidant gene expression in the presence of APAP. These data provide an experimental basis for the use of FMN in the treatment of patients with APAP-induced hepatotoxicity. PMID:28234915

  7. CHOLECYSTITIS AS A CAUSE OF ABDOMINAL PAIN IN PATIENTS WITH ACUTE VIRAL HEPATITIS A AND B

    Directory of Open Access Journals (Sweden)

    Miodrag Radunović

    2012-03-01

    Full Text Available Acute cholecystitis is an inflammation of the gallbladder wall, usually caused by gallstones in the cystic duct, which causes attacks of severe pain. At least 95% of the population with acute inflammation of the gallbladder have gallstones. Acute viral hepatitis is the liver inflammation accompanied by nausea, faintness, vomiting, pain below the right rib arch, jaundice. The presence of acute cholecystitis intensifies the existing symptoms. The aim of the paper was to show the incidence of the gallbladder inflammation in patients with acute hepatitis A or B. This retrospective-prospective study involved 110 patients treated for viral hepatitis A or B and had severe abdominal pain during hospitalization. The selected sample involved more male examinees - 63 (62% compared to female ones - 47 (38%. The most frequent age of examinees was 30-50 years, 82 (83%, and cholecystitis during hepatitis was also most common in the age group 30-50 years, 28 (73% patients. Cholecystitis was more common in patients with acute hepatitis B - 21 (55% examinees than in patients with acute hepatitis A - 17 (45% examinees. Ultrasound examination, performed in 24 (63% examinees showed gallstones in inflamed gallbladder, while 14 (37% examinees had the inflammation of the gallbladder without gallstones. The most common cause of severe abdominal pain in patients with acute liver infection caused by HAV and HBV infection was the gallbladder, 38 (34.5% patients. Cholecystitis was more common in patients with acute hepatitis B, 21 (55% examinees, than in those with an acute hepatitis A, 17 (45% examinees.

  8. Outbreak of acute hepatitis C following the use of anti-hepatitis C virus--screened intravenous immunoglobulin therapy

    OpenAIRE

    Healey, C J; Sabharwal, N K; Daub, J.; Davidson, F; Yap, P L; Fleming, K A; Chapman, R. W.; Simmonds, P; Chapel, H

    1996-01-01

    Hepatitis C virus (HCV) infection has been associated with intravenous (IV) immunoglobulin (Ig), and plasma donations used to prepare IV Ig are now screened to prevent transmission. Thirty-six patients from the United Kingdom received infusions from a batch of anti-HCV antibody-screened intravenous Ig (Gammagard; Baxter Healthcare Ltd., Thetford, Norfolk, England) that was associated with reports of acute hepatitis C outbreak in Europe. The aim of this study was to document the epidemiology o...

  9. Protective Activity of Total Polyphenols from Genista quadriflora Munby and Teucrium polium geyrii Maire in Acetaminophen-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Baali, Nacera; Belloum, Zahia; Baali, Samiya; Chabi, Beatrice; Pessemesse, Laurence; Fouret, Gilles; Ameddah, Souad; Benayache, Fadila; Benayache, Samir; Feillet-Coudray, Christine; Cabello, Gérard; Wrutniak-Cabello, Chantal

    2016-04-01

    Oxidative stress is a major cause of drug-induced hepatic diseases and several studies have demonstrated that diet supplementation with plants rich in antioxidant compounds provides a variety of health benefits in these circumstances. Genista quadriflora Munby (Gq) and Teucrium polium geyrii Maire (Tp) are known to possess antioxidant and numerous biological properties and these endemic plants are often used for dietary or medicinal applications. Herein, we evaluated the beneficial effect of rich-polyphenol fractions of Gq and Tp to prevent Acetaminophen-induced liver injury and investigated the mechanisms involved in this protective action. Rats were orally administered polyphenolic extracts from Gq or Tp (300 mg/kg) or N-acetylcysteine (NAC: 200 mg/kg) once daily for ten days prior to the single oral administration of Acetaminophen (APAP: 1 g/kg). The results show that preventive administration of polyphenolic extracts from Gq or Tp exerts a hepatoprotective influence during APAP treatment by improving transaminases leakage and liver histology and stimulating antioxidant defenses. Besides, suppression of liver CYP2E1, GSTpi and TNF-α mRNA levels, with enhancement of mitochondrial bioenergetics may contribute to the observed hepatoprotection induced by Gq and Tp extracts. The effect of Tp extract is significantly higher (1.5-2 fold) than that of Gq extract and NAC regarding the enhancement of mitochondrial functionality. Overall, this study brings the first evidence that pretreatment with these natural extracts display in vivo protective activity against APAP hepatotoxicity through improving mitochondrial bioenergetics, oxidant status, phase I and II enzymes expression and inflammatory processes probably by virtue of their high total polyphenols content.

  10. Protective Activity of Total Polyphenols from Genista quadriflora Munby and Teucrium polium geyrii Maire in Acetaminophen-Induced Hepatotoxicity in Rats

    Science.gov (United States)

    Baali, Nacera; Belloum, Zahia; Baali, Samiya; Chabi, Beatrice; Pessemesse, Laurence; Fouret, Gilles; Ameddah, Souad; Benayache, Fadila; Benayache, Samir; Feillet-Coudray, Christine; Cabello, Gérard; Wrutniak-Cabello, Chantal

    2016-01-01

    Oxidative stress is a major cause of drug-induced hepatic diseases and several studies have demonstrated that diet supplementation with plants rich in antioxidant compounds provides a variety of health benefits in these circumstances. Genista quadriflora Munby (Gq) and Teucrium polium geyrii Maire (Tp) are known to possess antioxidant and numerous biological properties and these endemic plants are often used for dietary or medicinal applications. Herein, we evaluated the beneficial effect of rich-polyphenol fractions of Gq and Tp to prevent Acetaminophen-induced liver injury and investigated the mechanisms involved in this protective action. Rats were orally administered polyphenolic extracts from Gq or Tp (300 mg/kg) or N-acetylcysteine (NAC: 200 mg/kg) once daily for ten days prior to the single oral administration of Acetaminophen (APAP: 1 g/kg). The results show that preventive administration of polyphenolic extracts from Gq or Tp exerts a hepatoprotective influence during APAP treatment by improving transaminases leakage and liver histology and stimulating antioxidant defenses. Besides, suppression of liver CYP2E1, GSTpi and TNF-α mRNA levels, with enhancement of mitochondrial bioenergetics may contribute to the observed hepatoprotection induced by Gq and Tp extracts. The effect of Tp extract is significantly higher (1.5–2 fold) than that of Gq extract and NAC regarding the enhancement of mitochondrial functionality. Overall, this study brings the first evidence that pretreatment with these natural extracts display in vivo protective activity against APAP hepatotoxicity through improving mitochondrial bioenergetics, oxidant status, phase I and II enzymes expression and inflammatory processes probably by virtue of their high total polyphenols content. PMID:27043622

  11. Acute viral hepatitis in Lebanon: evidence for a HAV-like non-A non-B hepatitis.

    Science.gov (United States)

    Shamma'a, M H

    1984-02-01

    Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (less than 1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (greater than 14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.

  12. Non-hepatic insults are common acute precipitants in patients with acute on chronic liver failure (ACLF).

    Science.gov (United States)

    Duseja, Ajay; Chawla, Y K; Dhiman, R K; Kumar, Amit; Choudhary, Narendra; Taneja, Sunil

    2010-11-01

    Acute-on-chronic liver failure (ACLF) is a newly coined term to describe simultaneous coexistence of two liver conditions, one of them being chronic or long-standing and the other acute or recent. There is limited data on the entity of ACLF. This study was performed to review our experience in ACLF patients from a tertiary care centre. ACLF was defined as per the Asian Pacific Association for the Study of the Liver (APASL) criteria, except for including the non-hepatic insults as precipitating events. Based on the type of acute insult, patients were divided into type I (non hepatic injury) and type II (hepatic injury-further divided in to IIA-acute viral hepatitis (AVH) on underlying chronic liver disease (CLD), IIB-other acute hepatitic insults like drugs/toxins and IIC-same disease responsible for worsening). Patients were also analyzed for the mode of presentation, severity of liver illness, presence of acute kidney injury and other organ failure, hospital stay and final outcome. One hundred two patients with ACLF (85 males, mean age 44 ± 12.5 years) were included in the study; they accounted for 49% of all liver failures and 27% of all admissions during the study period. Sixty patients (59%) had known cirrhosis whereas 42 (41%) patients presented for the first time as ACLF, unaware of the underlying CLD. Sixty-two (60%) patients had type I ACLF while 40 (40%) patients had type II ACLF. Infections (47%) were the most common non-hepatic causes of acute deterioration in type I ACLF. Amongst type II, acute viral hepatitis (IIA) accounted for six patients (4 hepatitis E virus, 2 hepatitis A virus) and type II C was the most common with alcoholic hepatitis accounting for 30 (29%) patients. Acute kidney injury was present in 47 (46%) and hypotension in 36 (35%) patients. Hypoxemia with ventilatory support was required in 22 (21%) patients. Mean hospital stay of patients was 9.7 ± 6 days (2-27 days). Forty-seven (46%) patients either died or left hospital in a very

  13. Acute Viral Hepatitis A – Clinical, Laboratory and Epidemiological Characteristics

    Directory of Open Access Journals (Sweden)

    Melinda HORVAT

    2013-06-01

    Full Text Available Background and Aims: Infection with hepatitis A virus is still one of the most common causes of hepatitis worldwide. The clinical manifestation of acute hepatitis A (AHA in adults can vary greatly, ranging from asymptomatic infection to severe and fulminant hepatitis. The aim of this study was to describe the demographic, clinical characteristics, laboratory features and hospital outcome of adult patients with AHA over a consecutive period of 4 years within an area from Eastern European country. Methods: Two hundred and two adult patients diagnosed with AHA were retrospective, observational and analytic analized over a period of 4 years. Based on prothrombin time less than 50, the study group was stratified in medium (79.2% and severe forms (20.8%. We investigated the clinical, laboratory and epidemiological features. Statistical analysis were applied to compare the medium and severe forms of AHA. Results: Most patients (72.7% were younger than 40 years. The main symptoms included: dyspepsia (72.07%, jaundice (86.63%, asteno-adynamia (86.72%, and flu-like symptoms (53.46%. The hemorrhagic cutaneous-mucous manifestations (6.93% associated with the severe forms of AHA (OR =12.19, 95%CI -3.59 - 41.3, p =0.001. We found statistically significant differences for PT (p <0.001, INR (p <0.001, TQ (p <0.001, ALAT (p <0.001, ASAT (p <0.001, ALP (p <0.001 and platelets (p =0.009 between severe and medium AHA forms. We found that TQ, INR, ALAT and ASAT have the highest diagnostic values, statistically significant (p <0.05 for severe AHA forms with AUC (0.99, 0.99, 0.72, 0.70 at values of sensitivity (95%, 90.5%, 89%, 95% and specificity (98%, 99%, 88%,94%. Conclusions Medium severity AHA forms were found in most of the study group patients (79.2%. The severe AHA forms were associated with hemorrhagic cutaneous-mucous manifestations (OR =12.19, p =0.001. The univariate analysis proved a negatively statistically significant correlation between IP and ALAT

  14. Hepatitis e and acute liver failure in pregnancy.

    Science.gov (United States)

    Shalimar; Acharya, Subrat K

    2013-09-01

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

  15. Enhancement of acetaminophen-induced chronic hepatotoxicity in restricted fed rats: a nonclinical approach to acetaminophen-induced chronic hepatotoxicity in susceptible patients.

    Science.gov (United States)

    Kondo, Kazuma; Yamada, Naohito; Suzuki, Yusuke; Toyoda, Kaoru; Hashimoto, Tatsuji; Takahashi, Akemi; Kobayashi, Akio; Shoda, Toshiyuki; Kuno, Hideyuki; Sugai, Shoichiro

    2012-01-01

    Acetaminophen (APAP) is a commonly used and effective analgesic and antipyretic agent. However, some patients encounter hepatotoxicity after repeated APAP dosing at therapeutic doses. In the present study, we focused on the nutritional state as one of the risk factors of APAP-induced chronic hepatotoxicity in humans and investigated the contribution of undernourishment to susceptibility to APAP-induced chronic hepatotoxicity using an animal model mimicking undernourished patients. Rats were divided into 2 groups: the ad libitum fed (ALF) and the restricted fed (RF) rats and were assigned to 3 groups (n = 8/group) for each feeding condition. The animals were given APAP at 0, 300 and 500mg/kg for 99 days under each feeding condition. Plasma and urinary glutathione-related metabolites and liver function parameters were measured during the dosing period and hepatic glutathione levels were measured at the end of the dosing period. In the APAP-treated ALF rats hepatic glutathione levels were increased and hepatic function parameters were not changed, but in the APAP-treated RF rats hepatic glutathione levels were decreased at 500mg/kg and hepatic function parameters were increased at 300 and 500mg/kg. Moreover the urinary endogenous metabolite profile after long-term treatment with APAP in the ALF and RF rats was similar to that in human non-responders and responders to APAP-induced chronic hepatotoxicity, respectively. In conclusion, the RF rats were more sensitive to APAP-induced chronic hepatotoxicity than the ALF rats and were considered to be a useful model to estimate the contribution of the nutritional state of patients to APAP-induced chronic hepatotoxicity.

  16. Protective effects of hydrogen sulfide anions against acetaminophen-induced hepatotoxicity in mice.

    Science.gov (United States)

    Ishii, Isao; Kamata, Shotaro; Hagiya, Yoshifumi; Abiko, Yumi; Kasahara, Tadashi; Kumagai, Yoshito

    2015-12-01

    The key mechanism for hepatotoxicity resulting from acetaminophen (APAP) overdose is cytochrome P450-dependent formation of N-acetyl-p-benzoquinone imine (NAPQI), a potent electrophilic metabolite that forms protein adducts. The fundamental roles of glutathione in the effective conjugation/clearance of NAPQI have been established, giving a molecular basis for the clinical use of N-acetylcysteine as a sole antidote. Recent evidence from in vitro experiments suggested that sulfide anions (S(2-)) to yield hydrogen sulfide anions (HS(-)) under physiological pH could effectively react with NAPQI. This study evaluated the protective roles of HS(-) against APAP-induced hepatotoxicity in mice. We utilized cystathionine γ-lyase-deficient (Cth(-/-)) mice that are highly sensitive to acetaminophen toxicity. Intraperitoneal injection of acetaminophen (150 mg/kg) into Cth(-/-) mice resulted in highly elevated levels of serum alanine/aspartate aminotransferases and lactate dehydrogenase associated with marked increases in oncotic hepatocytes; all of which were significantly inhibited by intraperitoneal preadministration of sodium hydrosulfide (NaHS). NaHS preadministration significantly suppressed APAP-induced serum malondialdehyde level increases without abrogating APAP-induced rapid depletion of hepatic glutathione. These results suggest that exogenous HS(-) protects hepatocytes by directly scavenging reactive NAPQI rather than by increasing cystine uptake and thereby elevating intracellular glutathione levels, which provides a novel therapeutic approach against acute APAP poisoning.

  17. Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis.

    Science.gov (United States)

    Baatarkhuu, Oidov; Lee, Hye Won; George, Jacob; Munkh-Orshikh, Dashchirev; Enkhtuvshin, Baasankhuu; Ariunaa, Sosorbaram; Eslam, Mohammed; Ahn, Sang Hoon; Han, Kwang-Hyub; Kim, Do Young

    2017-06-01

    Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.

  18. Inhibitor of apoptosis signal-regulating kinase 1 protects against acetaminophen-induced liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yuchao; Ramachandran, Anup [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Breckenridge, David G.; Liles, John T. [Department of Biology, Gilead Sciences, Inc., Foster City, CA (United States); Lebofsky, Margitta [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Farhood, Anwar [Department of Pathology, St. David' s North Austin Medical Center, Austin, TX 78756 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-07-01

    Metabolic activation and oxidant stress are key events in the pathophysiology of acetaminophen (APAP) hepatotoxicity. The initial mitochondrial oxidative stress triggered by protein adduct formation is amplified by c-jun-N-terminal kinase (JNK), resulting in mitochondrial dysfunction and ultimately cell necrosis. Apoptosis signal-regulating kinase 1 (ASK1) is considered the link between oxidant stress and JNK activation. The objective of the current study was to assess the efficacy and mechanism of action of the small-molecule ASK1 inhibitor GS-459679 in a murine model of APAP hepatotoxicity. APAP (300 mg/kg) caused extensive glutathione depletion, JNK activation and translocation to the mitochondria, oxidant stress and liver injury as indicated by plasma ALT activities and area of necrosis over a 24 h observation period. Pretreatment with 30 mg/kg of GS-459679 almost completely prevented JNK activation, oxidant stress and injury without affecting the metabolic activation of APAP. To evaluate the therapeutic potential of GS-459679, mice were treated with APAP and then with the inhibitor. Given 1.5 h after APAP, GS-459679 was still protective, which was paralleled by reduced JNK activation and p-JNK translocation to mitochondria. However, GS-459679 treatment was not more effective than N-acetylcysteine, and the combination of GS-459679 and N-acetylcysteine exhibited similar efficacy as N-acetylcysteine monotherapy, suggesting that GS-459769 and N-acetylcysteine affect the same pathway. Importantly, inhibition of ASK1 did not impair liver regeneration as indicated by PCNA staining. In conclusion, the ASK1 inhibitor GS-459679 protected against APAP toxicity by attenuating JNK activation and oxidant stress in mice and may have therapeutic potential for APAP overdose patients. - Highlights: • Two ASK1 inhibitors protected against acetaminophen-induced liver injury. • The ASK1 inhibitors protect when used as pre- or post-treatment. • Protection by ASK1 inhibitor is

  19. Acute hepatitis due to hepatitis A virus subgenotype IA as an imported infectious disease from Indonesia.

    Science.gov (United States)

    Utsumi, Takako; Yano, Yoshihiko; Amin, Mochamad; Lusida, Maria I; Soetjipto; Hotta, Hak; Hayashi, Yoshitake

    2014-10-01

    A 25-year-old Japanese man was admitted with general malaise and fever, which had developed 12 days after coming back to Japan from Indonesia. Blood examination revealed elevated transaminase levels and positivity for the IgM anti-HAV antibody; therefore, he was diagnosed with acute hepatitis A. HAV-RNA was detected in his serum and phylogenetically classified as subgenotype IA. The partial genome in the VP1/P2A region was consistent with the strain recently isolated from Surabaya, which indicated that he had been infected during his stay in Indonesia. Thus, HAV vaccination is recommended before visiting HAV-endemic countries for a long period of time.

  20. "Pseudotumoral" hepatic pattern in acute alcoholic hepatitis:A case report

    Institute of Scientific and Technical Information of China (English)

    Andrea Tenca; Sara Massironi; Agostino Colli; Guido Basilisco; Dario Conte

    2009-01-01

    In acute alcoholic hepatitis (AAH),a "pseudotumoral" appearance of the liver parenchyma on computed tomography (CT) scan has been reported.The main findings are hypervascularized areas closely similar to those observed in large hepatocellular carcinomas.We report a case of a patient affected by AAH with an unusual appearance of these "pseudotumoral" areas on CT scan,close resembling a metastatic cancer rather than a primary hepatocellular carcinoma.In fact,in contrast with previous reports,the picture was characterized by the presence of many inhomogeneous,hypoattenuated areas highlighted during both pre-and post-contrast phases.Moreover,we report the first description of "pseudotumoral" lesions on ultrasound scan.This patient was successfully treated with corticosteroids,even if many controversies still exist regarding their efficacy in this setting.

  1. Evaluation of the Hepatoprotective Effects of Lantadene A, a Pentacyclic Triterpenoid of Lantana Plants against Acetaminophen-induced Liver Damage

    Directory of Open Access Journals (Sweden)

    Sreenivasan Sasidharan

    2012-11-01

    Full Text Available The aim of the present study was to evaluate the hepatoprotective activity of lantadene A against acetaminophen-induced liver toxicity in mice was studied. Activity was measured by monitoring the levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP and bilirubin, along with histo-pathological analysis. Silymarin was used as positive control. A bimodal pattern of behavioural toxicity was exhibited by the lantadene A-treated group at the beginning of the treatment. However, treatment with lantadene A and silymarin resulted in an increase in the liver weight compared with the acetaminophen treated group. The results of the acetaminophen-induced liver toxicity experiments showed that mice treated with lantadene A (500 mg/kg showed a significant decrease in the activity of ALT, AST and ALP and the level of bilirubin, which were all elevated in the acetaminophen treated group (p < 0.05. Histological studies supported the biochemical findings and a maximum improvement in the histoarchitecture was seen. The lantadene A-treated group showed remarkable protective effects against histopathological alterations, with comparable results to the silymarin treated group. The current study confirmed the hepatoprotective effects of lantadene A against the model hepatotoxicant acetaminophen, which is likely related to its potent antioxidative activity.

  2. Typhoid Fever Presenting With Acute Renal Failure And Hepatitis Simultaneously - A Rare Presentation

    OpenAIRE

    Rajput R.; Jain D; Kumar A.; Mittal A

    2016-01-01

    Typhoid fever is an important health problem worldwide but its incidence is more in developing countries. Hepatic involvement is common, but both hepatic and renal involvement is rare in typhoid fever. We report a case of typhoid fever presenting with hepatitis and acute renal failure. A 17 year old male presenting with fever and pain abdomen was found to have raised blood urea, creatinine, liver enzymes and bilirubin. Widal and typhidot (IgM,IgG) test were positive. His symptoms subsided and...

  3. Injections given in healthcare settings as a major source of acute hepatitis B in Moldova.

    Science.gov (United States)

    Hutin, Y J; Harpaz, R; Drobeniuc, J; Melnic, A; Ray, C; Favorov, M; Iarovoi, P; Shapiro, C N; Woodruff, B A

    1999-08-01

    Two case-control studies were conducted between January 1994 and August 1995 to determine the relative importance of injections and other exposures as a source of acute hepatitis B in Moldova among adults (aged 15 years) and children (aged 2-15 years). Results showed that injections in various health care settings were associated with acute hepatitis B and showed a higher proportion among adults compared with children. Contact with an HBsAg-positive person was also associated with illnesses; however, there was no statistically significant association between acute hepatitis B and other exposures. The risk of HBV transmission following percutaneous exposure is high (at least 30%). Calculation of the population attributable to risk suggests that injections associated with acute hepatitis B cases occurred in adults (52%) and children (21%). Adverse effects of injections may not be apparent in causing chronic infections. Transmission of blood-borne pathogens through unsafe injection practices is a problem increasingly identified worldwide.

  4. Evaluation of adults with acute viral hepatitis a and review of the literature.

    Science.gov (United States)

    Tekin, R; Yolbas, I; Dal, T; Demirpençe, Ö; Kaya, S; Bozkurt, F; Deveci, Ö; Çelen, M K; Tekin, A

    2013-01-01

    In developing countries HAV infection is very common in the first years of life and it is often asymptomatic. However especially in regions of intermediate endemicity, exposure to the virus may delay and outbreaks of hepatitis A may be encountered in adults. The aim of this study is to evaluate the clinical and laboratory findings and risk factors of adults with acute viral hepatitis A. In present study we evaluated 203 patient with acute viral hepatitis A, who were admitted to four different hospitals of three cities of Turkey between January 2000-December 2011, retrospectively. The diagnosis of acute viral hepatitis A was performed by laboratory findings and clinically. In a total of 203 patients, 120 (59.1%) patients were male and 83 (40.9%) were female. Mean age of cases with acute viral hepatitis A was 24.7 +11.8 years (ranged 15 to 82 years old). Acute viral hepatitis A were seen in patient who were 15-20 years and 21-30 years old, commonly. Jaundice (74%), fatigue (68%), nausea- vomiting (56%) and dark urine (48%) were the most common symptoms in cases. Prolonged cholestasis (6.8%) was the most common atypical manifestation. Prolonged jaundice was more frequent in the cases with positive HBsAg (P viral hepatitis A can cause atypical presentations such as prolonged cholestasis, acute kidney injury and fulminant hepatitis. Some precautions such as routine vaccination program, improvement of hygiene conditions and informing people about it, should be taken for reducing of acute viral hepatitis A infection incidence.

  5. IMMUNOHISTOCHEMICAL STUDY OF EXTRACELLULAR-MATRIX IN ACUTE GALACTOSAMINE HEPATITIS IN RATS

    NARCIS (Netherlands)

    JONKER, AM; DIJKHUIS, FWJ; BOES, A; HARDONK, MJ

    1992-01-01

    A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fi

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

    NARCIS (Netherlands)

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

    1990-01-01

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

  7. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

    National Research Council Canada - National Science Library

    Evangelista Sagnelli Caterina Sagnelli Mariantonietta Pisaturo Margherita Macera Nicola Coppola

    2014-01-01

    The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984...

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

    Science.gov (United States)

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

    2014-11-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the King's College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and recovered. Careful investigation identified imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010 affecting 13 patients. Virus sequence analysis of our patient's virus showed a strain commonly found in Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute liver failure, and hepatitis A vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Urticaria and Periorbital Edema as Prodromal Presenting Signs of Acute Hepatitis B Infection

    NARCIS (Netherlands)

    van Aalsburg, Rob; de Pagter, Anne P. J.; van Genderen, Perry J.

    2011-01-01

    A 34-year-old patient presented with giant, transient urticarial skin lesions and periorbital edema after a 3-month stay in DR Congo. Retrospective analysis of stored samples revealed that these signs were prodromal manifestations of acute hepatitis B infection. The hepatitis B infection was

  10. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

    Science.gov (United States)

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P hepatitis A.

  11. Ultrasonographic Findings of the Gallbladder in Patients with Acute Hepatitis A: Do They Have Clinical Relevance?

    Energy Technology Data Exchange (ETDEWEB)

    An, Ji Young; Kim, Hyoung Jung; Lee, Dong Ho; Lim, Joo Won; Ko, Young Tae; Choi, Bong Keun [Dept. of Radiology, Graduate School of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul (Korea, Republic of)

    2012-06-15

    To determine the association of gallbladder (GB) abnormalities on ultrasonography (US) of patients with acute hepatitis A with demographic, clinical, and biochemical factors, and with other US findings. This retrospective study was approved by our institutional review board, which waived the requirement for informed consent. We retrospectively evaluated 152 consecutive patients with acute hepatitis A who underwent US. The diagnosis of acute hepatitis A was made during acute illness by demonstrating anti- HAV of the IgM class. US images were reviewed simultaneously by two abdominal radiologists and a consensus was reached for GB wall thickening, GB collapse, lymphadenopathy, and hepatic echogenicity. The associations between demographic, clinical, biochemical, and US findings and GB wall thickening or collapse were then assessed. GB wall thickening was present in 123 (81%) and GB collapse in 96 (63%) of the 152 patients. Total bilirubin level and GB collapse differed significantly (p < 0.05) between patients with and without GB wall thickening. Gender ratio, total and peak total bilirubin level, and GB wall thickness differed significantly (p < 0.05) between patients with and without GB collapse. Multivariate analysis showed that GB wall thickening was associated with GB collapse and vice versa. GB wall thickening and GB collapse are common US abnormalities associated with each other in patients with acute hepatitis A. However, GB wall thickening or collapse is not associated with any demographic, clinical, or biochemical factors, or with other US findings, in patients with acute hepatitis A.

  12. An Outbreak of Acute Hepatitis Caused by Genotype IB Hepatitis A Viruses Contaminating the Water Supply in Thailand.

    Science.gov (United States)

    Ruchusatsawat, Kriangsak; Wongpiyabovorn, Jongkonnee; Kawidam, Chonthicha; Thiemsing, Laddawan; Sangkitporn, Somchai; Yoshizaki, Sayaka; Tatsumi, Masashi; Takeda, Naokazu; Ishii, Koji

    2016-01-01

    In 2000, an outbreak of acute hepatitis A was reported in a province adjacent to Bangkok, Thailand. To investigate the cause of the 2000 hepatitis A outbreaks in Thailand using molecular epidemiological analysis. Serum and stool specimens were collected from patients who were clinically diagnosed with acute viral hepatitis. Water samples from drinking water and deep-drilled wells were also collected. These specimens were subjected to polymerase chain reaction (PCR) amplification and sequencing of the VP1/2A region of the hepatitis A virus (HAV) genome. The entire genome sequence of one of the fecal specimens was determined and phylogenetically analyzed with those of known HAV sequences. Eleven of 24 fecal specimens collected from acute viral hepatitis patients were positive as determined by semi- nested reverse transcription PCR targeting the VP1/2A region of HAV. The nucleotide sequence of these samples had an identical genotype IB sequence, suggesting that the same causative agent was present. The complete nucleotide sequence derived from one of the samples indicated that the Thai genotype IB strain should be classified in a unique phylogenetic cluster. The analysis using an adjusted odds ratio showed that the consumption of groundwater was the most likely risk factor associated with the disease. © 2017 S. Karger AG, Basel.

  13. Liquid chromatography mass spectrometry-based profiling of phosphatidylcholine and phosphatidylethanolamine in the plasma and liver of acetaminophen-induced liver injured mice.

    Science.gov (United States)

    Ming, Ya-Nan; Zhang, Jing-Yi; Wang, Xiao-Lin; Li, Chun-Min; Ma, Si-Cong; Wang, Zheng-Yang; Liu, Xiao-Lin; Li, Xiao-Bo; Mao, Yi-Min

    2017-08-14

    Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver. The expressions of phosphatidylcholine and phosphatidylethanolamine metabolism related genes in liver were detected by quantitative Reverse transcription polymerase chain reaction (qRT-PCR) and Western-blot. Following Acetaminophen treatment, the content of many PC and PE species in plasma increased from 1 h time point, peaked at 3 h or 6 h, and tended to return to baseline at 24 h time point. The relative contents of almost all PC species in liver decreased from 1 h, appeared to be lowest at 6 h, and then return to normality at 24 h, which might be partly explained by the suppression of phospholipases mRNA expressions and the induction of choline kinase (Chka) expression. Inconsistent with PC profile, the relative contents of many PE species in liver increased upon Acetaminophen treatment, which might be caused by the down-regulation of phosphatidylethanolamine N-methyltransferase (Pemt). Acetaminophen overdose induced dramatic change of many PC and PE species in plasma and liver, which might be caused by damaging hepatocytes and interfering the phospholipid metabolism in Acetaminophen -injured liver.

  14. [Acute pancreatitis and acalculous cholecystitis associated with viral hepatitis A].

    Science.gov (United States)

    Arcana, Ronald; Frisancho, Oscar

    2011-01-01

    We report the case of a 14 year-old male from Lima. He is a student with a history of bronchial asthma since age 4 receives conditional salbutamol, corticosteroids used for asthma attacks (a crisis in 2010, 1 month ago) Refuses surgery or transfusions. He presented with a two weeks for abdominal pain, nausea, fever, and jaundice. Epigastric pain is colicky and radiated back to righ upper quadrant, refers in addition to nausea and fever, for ten days notice jaundice of skin and sclera. On examen he was lucid, with jaundice of skin and mucous membranes. There was no palpable lymph nodes, abdomen with bowel sounds, soft, depressible, liver span of 15cm, positive Murphy, no peritonitis. The laboratory findings showed hemoglobin 13gr, MCV 90, platelets 461.000/mm3, WBC 4320/mm, lymphocytes 1700 (39%). total bilirubin: 8.8, B Direct: 7.6, ALT (alanine aminotransferase): 3016, AST (aspartate aminotransferase): 984, alkaline phosphatase: 250, albumin: 3.34gr%, globulin: 2.8, amylase: 589 (high serum amylase), TP: 17, INR: 1.6, VHA IgM positive. 89 mg glucose, urea 19 mg%, creatinine 0.5 mg Hemoglobin 13gr, MCV 90 Platelet 461000/mm3, WBC 4320/mm, Lymphocytes 1700 (39%). The nuclear magnetic resonance showed hepatomegaly associated with thickening of gallbladder wall without stones up to 11mm inside. No bile duct dilatation, bile duct 4mm, pancreas increased prevalence of body size. Mild splenomegaly and free fluid in the space of Morrison and right flank. Abdominal ultrasound revealed a gallbladder wall thickness (11mm), without stones in his light. Pancreas to increase volume with peripancreatic fluid free perivesicular with a volume of 430 cc. Findings consistent with acute acalculous cholecystitis and acute pancreatitis. CT-scan showed enlarged pancreas with predominance of body and tail with peripancreatic edema; the gallbladder was thickening. We report this case because the extrahepatic manifestations of viral hepatitis A infection are uncommon, specially the

  15. Thrombocytopenic purpura as initial presentation of acute hepatitis A.

    Science.gov (United States)

    Scott, Julius Xavier; Gnananayagam, Ebor Jacob; Gupta, Sanjay; Simon, Anna; Mukhopadhya, Ashish

    2003-01-01

    Extrahepatic immune manifestations are rare in hepatitis A virus infection. We report a 4 1/2-year-old girl who presented with thrombocytopenic purpura as initial manifestation of hepatitis A virus infection. She responded to steroid therapy.

  16. Acute hepatitis C: changing epidemiology and association with HIV infection.

    Science.gov (United States)

    Brejt, Nick; Gilleece, Yvonne; Fisher, Martin

    2007-03-01

    Over the past 6 to 7 years an increasing incidence of acute hepatitis C virus (AHCV) has been fuelled by two different changing epidemics: (1) a new resurgence of AHCV amongst intravenous drug users (IVDU); and (2) presumed sexually transmitted AHCV amongst predominantly HIV-positive men who have sex with men (MSM). Increasing incidence amongst IVDUs is likely to be a consequence of changing injecting behaviour, possibly related to changes in perception of HIV as well as HCV risk and consequences. Increasing incidence amongst MSM is likely to be a consequence of changing sexual practices, for example number of sexual partners and type of sexual behaviour, as well as increasing availability of recreational drugs associated with sexual risk-taking, and wider availability of casual sexual partners via the internet or sex-on-premises venues. It remains unclear whether the current outbreaks in MSM, predominantly seen in HIV-positive individuals, reflect a predisposition to AHCV secondary to HIV status per se, or whether this reflects differences in behaviour amongst HIV-positive versus HIV-negative MSM, or potentially increased screening (either routine or secondary to abnormal liver function tests) in HIV-positive MSM. The majority of individuals with AHCV are asymptomatic and therefore routine screening of individuals in at-risk groups with abnormal liver function tests should be considered. Previous historical studies suggest that individuals with concomitant HIV infection are far less likely than those without to spontaneously clear HCV. It is currently recommended that such individuals acutely infected with HCV should undergo monitoring of HCV viral load levels to determine whether spontaneous clearance is likely or whether the opportunity for early treatment should be considered.

  17. Infección aguda por el VHB Acute infection by Hepatitis B Virus

    Directory of Open Access Journals (Sweden)

    F. Alegre

    2004-01-01

    Full Text Available El espectro clínico de la infección aguda por el virus de la hepatitis B es muy amplio, con cuadros que van desde una hepatitis anictérica y subclínica a una hepatitis ictérica aguda grave e incluso, en algunos casos, a una hepatitis fulminante. El diagnóstico depende en gran medida del grado de sospecha clínica de la hepatitis, estableciéndose el origen etiológico por el virus B mediante el estudio de marcadores serológicos y/o DNA en sangre. Aunque en la mayor parte de los casos la evolución de la hepatitis aguda por virus B es favorable, con resolución espontánea de la clínica en 4-8 semanas, no es infrecuente en ciertos casos, sobre todo en la infancia, la progresión a hepatitis crónica. No existe ningún tratamiento específico para la infección aguda por virus B que reduzca su gravedad o prevenga su evolución a hepatitis crónica. Se recomienda, no obstante, el reposo relativo, y la administración de una dieta hipercalórica. En las hepatitis agudas graves debe indicarse ingreso hospitalario; en casos de hepatitis fulminante ingreso en UCI para monitorización intensiva y valoración de trasplante hepático si no se produce mejoría espontánea. En el presente artículo se revisa, de forma breve y esquemática, la clínica, el diagnóstico, el pronóstico y el tratamiento de la infección aguda por el virus de la hepatitis B.The clinical spectrum of acute hepatitis B virus infection is very broad, with clinical manifestations that range from anicteric and sub-clinical hepatitis to severe acute icteric hepatitis and even, in some cases, to fulminant hepatitis. Diagnosis depends to a large extent on the degree of clinical suspicion of hepatitis, establishing the aetiological origin of the B virus through the study of serological markers and/or DNA in the blood. Although in the majority of cases there is a favourable evolution of acute hepatitis B virus infection, with spontaneous resolution of the clinical manifestations

  18. N-acetyl cysteine therapy in acute viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Huseyin Gunduz; Oguz Karabay; Ali Tamer; Resat Ozaras; Ali Mert; Omer Fehmi Tabak

    2003-01-01

    AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P>0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

  19. Hepatic effect of NAC on sevear acute pancteatise of rats

    Institute of Scientific and Technical Information of China (English)

    Fang Chen; Ye-Jiang Zhou

    2014-01-01

    Objective:To analyze the hepatic protection of n-acetyl cysteine(NAC) on severe acute pancreatitis(SAP).Methods:SD rats were randomly divided into control group,SAP group and NAC group.SAPAHO method was adopted to establish the model,2 h after modeling, rats inNAC group had intraperitoneal injection ofNAC(200 mg/kg).Ten rats from each group were sacrificed in every6 and12 h at different time points respectively.Liver damage, liver function and serum amylase,AST,ALT and malondialdehyde(MDA) were determined.Results:Serum amylase,AST, ALT andMDA content inSAP,NAC group at each time point were significantly higher in the control group(P<0.05), serum amylase,AST,ALT andMDA content inNAC group rats were lower in theSAP group significantly(P<0.05);Microscopic examination showed that the liver injury in rats and theNAC group significantly reduced in theSAP group.Conclusions:NAC provides effective protection against liver damage toSAP, protective fromSAP liver injury.

  20. Acute hepatitis E by a new isolate acquired in the United States.

    Science.gov (United States)

    Kwo, P Y; Schlauder, G G; Carpenter, H A; Murphy, P J; Rosenblatt, J E; Dawson, G J; Mast, E E; Krawczynski, K; Balan, V

    1997-12-01

    To report the first case of acute hepatitis E by a novel isolate acquired in the United States and confirmed by nucleotide sequencing. We describe the clinical manifestations and the results of associated laboratory studies in a man who was found to have acute hepatitis E infection. A 62-year-old man was hospitalized because of fever, abdominal pain, and jaundice. After an initial evaluation did not provide a cause, his serum was found to be positive for IgG anti-hepatitis E virus (HEV) by three antibody assays. Serum was also positive for HEV RNA by reverse transcriptase polymerase chain reaction (PCR). Sequencing results from the PCR products demonstrated substantial differences at the nucleotide level between this strain and the known Mexican and Burmese strains. On the basis of this initial report, HEV should be considered an etiologic agent in patients with acute non-ABC hepatitis in the United States.

  1. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A

    Science.gov (United States)

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, Phepatitis A. PMID:26090677

  2. Serological profile of sporadic acute viral hepatitis in an area of hyper-endemic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Ayoola Ayobanji

    2001-01-01

    Full Text Available Background: Located in the south western part of Saudi Arabia, the Gizan region is largely a rural community in which hepatitis B and chronic liver disease including hepatocellular carcinoma are highly prevalent. Aim of study: To determine the relative frequencies of acute hepatitis A, B, C and E in acute viral hepatitis in an area of hyperendemic hepatitis B infection. Methods and materials: In a prospective study 246 consecutive patients (179 males and 67 females diagnosed in a 2-year period were tested for markers of Hepatitis A virus (HAV, hepatitis B virus (HBV, hepatitis C (HCV and hepatitis E virus (HEV. Results: Of the patients tested, 131 (53.3% were children (< 10 years, and 42 (17% were 11 - 20 years in age. Ig M anti -HAV, IgM anti-HBV, anti- HCV and IgM anti-HEV were positive in 37%, 19.1%, 3.7% and 13.7% respectively. Markers of these viruses were absent in 24.4%. Among 131 children (< 10 years the commonest cause of AVH was HAV occurring in 57.3% of the cases. In adults (> 21 years HBV was found in 35.6% and IgM anti -HAV was detected in only 6.8%. In contrast to the age- related decline in the frequency of acute HA, the proportion of acute HE were similar in all age groups (13.7% in children, 16.7% in adolescents and 11.0% in adults. Conclusion: The study indicated that HAV is still a common cause of AVH particularly among children in Gizan. Acute 1-113 had a low occurrence among the children, evidently as a consequence of the integration of HB vaccine into the Saudi Arabian national EPI, 10 years ago. With the availability of combined HB and HA vaccines, It should be possible to graft the vaccination against HAV on to the existing program in Saudi Arabia. Affecting 13.4% of the group studied, sporadic HEV constitute a significant cause of AVH in this population. Until HEV vaccine becomes widely available, its prevention would be mainly by the improvement of socio - economic and hygienic standards of the population.

  3. Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A

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    Husain Syed A

    2011-05-01

    Full Text Available Abstract Background Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. Objective In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. Methods Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. Results Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005 compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+ ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2% were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P Conclusions Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  5. Epidemiological aspects of acute viral hepatitis in São Paulo, Brazil

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    L. C. da Silva

    1986-12-01

    Full Text Available As few reports on the prevalence of each type of viral hepatitis have been published in our country, we studied 154 patients with acute viral hepatitis consecutively seen at the Liver Unit from November 1980 to November 1984. The frequency of hepatitis A, B and non-A, non-B was 52.6%, 27.3% and 20.1% respectively. Greater frequency in young people, previous contact with infected patients and ingestion of suspected foods were the predominant epidemiological features in the hepatitis A group. Hepatitis B was characterized by the parenteral, non-transfusional exposure, previous contact and a high occurence in health-care workers. A history of blood transfusion was a significant finding in the hepatitis non-A, non-B group. Finally, the routes of transmission were unknown in 30-40% of the three groups of patients.

  6. Lysosomal iron mobilization and induction of the mitochondrial permeability transition in acetaminophen-induced toxicity to mouse hepatocytes.

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    Kon, Kazuyoshi; Kim, Jae-Sung; Uchiyama, Akira; Jaeschke, Hartmut; Lemasters, John J

    2010-09-01

    Acetaminophen induces the mitochondrial permeability transition (MPT) in hepatocytes. Reactive oxygen species (ROS) trigger the MPT and play an important role in AAP-induced hepatocellular injury. Because iron is a catalyst for ROS formation, our aim was to investigate the role of chelatable iron in MPT-dependent acetaminophen toxicity to mouse hepatocytes. Hepatocytes were isolated from fasted male C3Heb/FeJ mice. Necrotic cell killing was determined by propidium iodide fluorometry. Mitochondrial membrane potential was visualized by confocal microscopy of tetramethylrhodamine methylester. Chelatable ferrous ion was monitored by calcein quenching, and 70 kDa rhodamine-dextran was used to visualize lysosomes. Cell killing after acetaminophen (10mM) was delayed and decreased by more than half after 6 h by 1mM desferal or 1mM starch-desferal. In a cell-free system, ferrous but not ferric iron quenched calcein fluorescence, an effect reversed by dipyridyl, a membrane-permeable iron chelator. In hepatocytes loaded with calcein, intracellular calcein fluorescence decreased progressively beginning about 4 h after acetaminophen. Mitochondria then depolarized after about 6 h. Dipyridyl (20mM) dequenched calcein fluorescence. Desferal and starch-desferal conjugate prevented acetaminophen-induced calcein quenching and mitochondrial depolarization. As calcein fluorescence became quenched, lysosomes disappeared, consistent with release of iron from ruptured lysosomes. In conclusion, an increase of cytosolic chelatable ferrous iron occurs during acetaminophen hepatotoxicity, which triggers the MPT and cell killing. Disrupted lysosomes are the likely source of iron, and chelation of this iron decreases acetaminophen toxicity to hepatocytes.

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

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    Rochling, Fedja

    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 renal failure after consuming street tacos in Central and South America while on a business trip. His protracted course required corticosteroid therapy, multiple sessions of plasma exchange, and numerous units of packed red blood cells. This case demonstrates the importance of vaccination in high-risk adults. A prompt diagnosis of acute hepatitis A virus infection is essential, as uncommon presentations may delay diagnosis leading to permanent morbidity and potentially death in fulminant cases. We also demonstrate the efficacy of treatment of cholestatic hepatitis A virus infection, hemolytic anemia, and renal failure with corticosteroids and plasma exchange. PMID:25431704

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

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    Robert T. Lapp

    2013-01-01

    Full Text Available 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 renal failure after consuming street tacos in Central and South America while on a business trip. His protracted course required corticosteroid therapy, multiple sessions of plasma exchange, and numerous units of packed red blood cells. This case demonstrates the importance of vaccination in high-risk adults. A prompt diagnosis of acute hepatitis A virus infection is essential, as uncommon presentations may delay diagnosis leading to permanent morbidity and potentially death in fulminant cases. We also demonstrate the efficacy of treatment of cholestatic hepatitis A virus infection, hemolytic anemia, and renal failure with corticosteroids and plasma exchange.

  9. Relationship between antioxidant capacity and oxidative stress in children with acute hepatitis A

    Institute of Scientific and Technical Information of China (English)

    Mustafa Cemek; Semiha Dede; Fahri Bayiro(g)lu; Hüseyin (C)aksen; Fatma Cemek; Nihat Mert

    2006-01-01

    AIM: To investigate in children with acute hepatitis A.According to our knowledge, there are no data about the blood levels of malondialdehyde (MDA, an indicator of oxidative stress) and nonenzymic antioxidants in children with acute hepatitis A.METHODS: Whole blood MDA and reduced glutathione (GSH), serum β-carotene, retinol, vitamin E and vitamin C levels were studied in 19 (10 females, 9 males)children with acute hepatitis A and in 29 (13 females, 16males) healthy control subjects.RESULTS: There was a statistically significant difference between patients and controls for all parameters (P <0.05). Lipid peroxidation marker MDA was significantly elevated (P < 0.001), while antioxidants β-carotene,retinol and GSH were significantly decreased (all P <0.001) in patients compared to healthy subjects. In addition, α-tocopherol and ascorbic acid levels were significantly lower in patients when compared to age and sex matched controls (P < 0.05, P < 0.01, respectively).CONCLUSION: Our study shows that hepatitis A virus induces oxidative stress in childern with hepatitis A. This finding could be taken into consideration to improve the therapeutic approach in acute hepatitis A.

  10. Clinical features of patients with acute exacerbation of chronic hepatitis B: an analysis of 74 cases

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    RUAN Jianwen

    2016-11-01

    Full Text Available ObjectiveTo investigate the clinical features of patients with acute exacerbation of chronic hepatitis B, and to provide a basis of evidence-based medicine for the diagnosis and treatment of acute exacerbation of chronic hepatitis B. MethodsA retrospective analysis was performed for the clinical data of 74 patients with acute exacerbation of chronic hepatitis B who were diagnosed in The People′s Hospital of Haikou from January 2011 to October 2015. These patients were divided into HBeAg positive group (51 patients and HBeAg negative group (23 patients. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsThe patients with acute onset of chronic hepatitis B had a level of alanine aminotransferase (ALT of 523-2940 U/L and were manifested as icteric hepatitis (64 patients, 86.49%, and 65 patients (87.84% were cured within 4 weeks. There were no significant differences in baseline ALT, aspartate aminotransferase, and HBV DNA levels between the HBeAg positive group and the HBeAg negative group (all P>0.05, and the HBeAg negative group had a significantly higher level of total bilirubin (TBil than the HBeAg positive group (141.1±132.9 μmol/L vs 80.1±68.8μmol/L, t=2.745, P=0.007. ConclusionThe acute exacerbation of chronic hepatitis B is similar to acute hepatitis B, and the patients with negative HBeAg have a high level of TBil and severe hepatocyte injury.

  11. Pancreatitis developing in the context of acute hepatitis: a literature review.

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    Khedmat, Hossein; Ghamar-Chehreh, Mohammad Ebrahim; Agah, Shahram; Aghaei, Aghdas

    2015-03-20

    Despite strong evidence suggestive of associations between hepatic diseases and pancreas injury, a potential relationship between acute hepatitis and acute pancreatitis has not been a matter of review; which we focused on in the current paper. Some of the main findings of this review article are: fulminant hepatitis failure represents the highest incident rate of hepatitis-related acute pancreatitis; so a screening program might be indicative in these patients. Specific characteristics of HAV-related pancreatitis are that it is a benign condition with no reported mortality; and a male preponderance in the incidence, with females developing in older ages and having shown the signs of both conditions simultaneously. The incidence of acute pancreatitis in HBV infection is the lowest, but the mortality was the highest. HEV-related acute pancreatitis was most likely to represent pseudocysts and there was an apparent ethnic-priority with Indian descents, the only reported cases in the literature. Hepatitis-related pancreatitis in liver transplant recipients was most frequent in HBV infected patients; and in IFN-induced pancreatitis, cessation of the drug was most effective in treatment, with no catastrophic event reported.

  12. Epidemiology of acute and chronic hepatitis B virus infection in Norway, 1992-2009

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    Blystad Hans

    2011-05-01

    Full Text Available Abstract Background Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk groups (intravenous drug users (IDUs, Men who have Sex with Men (MSM, immigrants and contacts of known carriers. We describe the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of current risk groups and recommend preventive measures. Methods We used case based data from the national surveillance system on acute and chronic hepatitis B. The Norwegian Statistics Bureau provided population and migration data and the Norwegian Institute for Alcohol and Drug Research the estimated number of active IDUs between 2002-2007. Incidence rates (IR and incidence rate ratios (IRR for acute hepatitis B and notification rates (NR and notification rate ratios (NRR for chronic hepatitis B with 95% confidence intervals were calculated. Results The annual IR of acute hepatitis B ranged from 0.7/100,000 (1992 to 10.6/100,000 (1999. Transmission occurred mainly among IDUs (64% or through sexual contact (24%. The risk of acquiring acute hepatitis B was highest in people aged 20-29 (IRR = 6.6 [3.3-13.3], and in males (IRR = 2.4 [1.7-3.3]. We observed two peaks of newly reported chronic hepatitis B cases in 2003 and 2009 (NR = 17.6/100,000 and 17.4/100,000, respectively. Chronic hepatitis B was more likely to be diagnosed among immigrants than among Norwegians (NRR = 93 [71.9-120.6], and among those 20-29 compared to those 50-59 (NRR = 5.2 [3.5-7.9]. Conclusions IDUs remain the largest risk group for acute hepatitis B. The observed peaks of chronic hepatitis B are related to increased immigration from high endemic countries and screening and vaccination of these groups is important to prevent further spread of infection. Universal screening of pregnant women should be introduced. A universal vaccination strategy should be considered, given the high cost of

  13. Chinese green tea and acute hepatitis: a rare yet recurring theme.

    Science.gov (United States)

    Lugg, Sebastian Thomas; Braganza Menezes, Darryl; Gompertz, Simon

    2015-09-23

    A previously healthy 16-year-old girl presented with signs of acute hepatitis. On initial enquiry, she had not taken any prescribed or 'over-the-counter' medications, and there was no recent travel history. Further investigations revealed no viral, autoimmune or metabolic cause of hepatitis. Only following specific questioning did she reveal that she had, in the preceding 3 months, regularly consumed internet ordered Chinese green tea, which contained Camellia sinensis. After ceasing green tea consumption, there was a rapid and sustained recovery of her hepatitis. The authors discuss the probable cause of herbal tea in this case of acute hepatitis, and the importance of awareness of this rare yet recurring theme for patients and clinicians alike.

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

    Science.gov (United States)

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

    2015-02-01

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

  15. [Acute hepatitis-associated pure red cell aplasia: a case report].

    Science.gov (United States)

    Della Loggia, Paolo; Cremonini, Laura

    2002-12-01

    After a holiday in Egypt, a 57-year-old caucasian woman developed acute hepatitis A. The illness seemed initially to have a benign course, with a decreasing trend of hepatic enzymes and an apparent recovery. Three weeks later a relapse occurred. Recurrence of symptoms and aminotransferase elevation were associated with severe anemia; a hyporegenerative anemia was diagnosed and all laboratory findings were consistent with pure red cell aplasia. The haematologic disorder was successfully treated with red cell transfusion and glucocorticoids.

  16. [Epidemiologic and clinical aspects of acute hepatitis B in the past decade].

    Science.gov (United States)

    Mihalache, Doina; Vâţă, Andrei; Vâţă, Alla; Corcaci, Carmen; Hurmuzache, M; Scurtu, Roxana

    2003-01-01

    To study the clinical and epidemiological aspects of acute B hepatitis during the last 11 years. We retrospectively studied 1712 patient files, admitted in the Department of Infectious Diseases Iaşi, with acute B hepatitis between 1992-2002. The majority of the patients (69%) had an urban origin. Teenagers and young adults were predominantly affected (59% had between 15 and 34 years). A point of entry of the pathogen was identified only in 20% of the patients. The mean incubation period was 4 month. 24% of the patients had a prolonged form of the disease (over 30 days of jaundice). A fulminant evolution was noted in 1.2% of cases. Extrahepatic involvement was described in 25% of the patients. The global mortality was 1.15%. The number of patients with acute B hepatitis decreased by half during the last 11 years.

  17. [Clinical and immunological features of acute hepatitis B in patients with concomitant chronic toxic liver damage].

    Science.gov (United States)

    Furyk, E; Ryabokon, E

    2013-02-01

    The article presents information obtained during the survey in 64 patients with acute hepatitis B. We show that acute hepatitis B in patients with concomitant chronic toxic liver characterized by a marked imbalance of cytokine status due to a lower level of interleukin-2 and a higher content of interleukin-8, the highest levels of nitrite content, spontaneous oxidative modifications of blood proteins and the lowest content of L -arginine in the blood serum in the dynamics of disease compared with patients without this concomitant factor. In the period of convalescence these changes in patients with acute hepatitis B with concomitant chronic toxic liver characterized combined with higher cytolysis of liver cells, often circulating in the blood of HBsAg seroconversion and less frequently with the advent of anti-HBeAg.

  18. Hepatitis E virus quasispecies and the outcome of acute hepatitis E in solid-organ transplant patients.

    Science.gov (United States)

    Lhomme, Sebastien; Abravanel, Florence; Dubois, Martine; Sandres-Saune, Karine; Rostaing, Lionel; Kamar, Nassim; Izopet, Jacques

    2012-09-01

    Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lower K(a)/K(s) ratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

  19. Prophylaxis of acute viral hepatitis by immune serum globulin, hepatitis B vaccine, and health education: a sixteen year study of Japan overseas cooperation volunteers.

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    Ohara, H; Ebisawa, I; Naruto, H

    1997-01-01

    From 1978 to 1993 a study of acute viral hepatitis contracted by the Japan Overseas Cooperation Volunteers (JOCV) during their assignments in tropical and subtropical countries was conducted. Of 10,509 subjects in this study, 240 cases of acute viral hepatitis were confirmed (hepatitis A = 139, hepatitis B = 72, and non-A, non-B hepatitis = 29). The annual morbidity was 5.1% in 1978 and 4.9% in 1979, with hepatitis A accounting for 80% of the cases. However, it decreased significantly after the prophylactic inoculation with immune serum globulin (ISG) was started in 1980. A significant decrease of hepatitis B from 1.2% in 1980 to 0.1% in 1990 was also seen after vaccination was introduced for all volunteers in 1988. Health education concerning food and water sanitation, and providing general information on viral hepatitis, was also conducted throughout this period. These results indicate that acute viral hepatitis could be successfully prevented in the JOCV with a combination of ISG, hepatitis B vaccination, and health education.

  20. Typhoid Fever Presenting With Acute Renal Failure And Hepatitis Simultaneously - A Rare Presentation

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    Rajput R.

    2016-05-01

    Full Text Available Typhoid fever is an important health problem worldwide but its incidence is more in developing countries. Hepatic involvement is common, but both hepatic and renal involvement is rare in typhoid fever. We report a case of typhoid fever presenting with hepatitis and acute renal failure. A 17 year old male presenting with fever and pain abdomen was found to have raised blood urea, creatinine, liver enzymes and bilirubin. Widal and typhidot (IgM,IgG test were positive. His symptoms subsided and deranged parameters resolved with treatment of typhoid fever.

  1. Review: Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xi-ping; WANG Lei; ZHANG Jie

    2007-01-01

    Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes ofvasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.

  2. Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B.

    Science.gov (United States)

    Shin, So Youn; Jeong, Sook-Hyang; Sung, Pil Soo; Lee, Jino; Kim, Hyung Joon; Lee, Hyun Woong; Shin, Eui-Cheol

    2016-05-01

    Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.

  3. [A case of sustained cholestasis caused by acute A viral hepatitis in Dubin-Johnson syndrome].

    Science.gov (United States)

    Ra, Sang Ho; Sung, Se Yong; Jung, Ho Yeon; Cha, Jae Hwang; Baik, Soon Koo; Cho, Mee Yon; Kim, Moon Young

    2012-04-01

    Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome.

  4. Acute enteral manganese intoxication with hepatic failure due to ingestion of a joint supplement overdose.

    Science.gov (United States)

    Borchers, Angela; Epstein, Steven E; Gindiciosi, Blaz; Cartoceti, Andrew; Puschner, Birgit

    2014-09-01

    Manganese is a ubiquitous, essential trace element and a common ingredient of joint supplement tablets. Little information is known about the inherent toxic potential if ingested at higher doses. A 5-year-old female spayed Pug dog presented for evaluation of vomiting and ataxia after accidental ingestion of approximately 100 joint supplement tablets. The dog developed acute hepatic failure and was euthanized 6 days after presentation due to progression of the disease. Necropsy showed severe acute hepatic necrosis. Liver and kidney samples were submitted for toxicology analysis, results of which showed severely elevated manganese concentrations in the liver and kidneys.

  5. Anxiety in mice with acute hepatic encephalopathy induced by thioacetamide

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    CHEN Qiming

    2014-10-01

    Full Text Available ObjectiveTo evaluate the mental disorders in mice with thioacetamide (TAA-induced acute hepatic encephalopathy (AHE. MethodsThirty male Kunming mice were equally and randomly divided into two groups (treatment group and control group. Mice in the treatment group received an intraperitoneal injection of TAA (200 mg·kg-1·d-1 for 3 days, up to 600 mg·kg-1, as compared with the same volume of physiological saline in the control group. Neurological function score, light/dark box, open field, and elevated plus-maze test were used to determine behavioral parameters at 24 h after the model was established. Serum ammonia, aspartate amino transferase (AST, alanine aminotransferase (ALT, and total bilirubin (TBil were measured at 24 h post determination of behavioral parameters. Comparison between two groups was made by independent-samples t test. ResultsIn the light/dark box test, the treatment group had significantly reduced residence time in the light box and number of shuttles between two boxes (t=-4.006, P<0.01; t=-2656, P<0.05; in the open field test, the treatment group had significantly reduced central distance, central time, and number of vertical movements (t=-3.639, P<0.05; t=-2.294, P<0.05; t=-2.282, P<0.05, as well as increased grooming time (t=5.992, P<0.01; meanwhile, the number of open-arm entries and residence time in the open arm for the treatment group were also reduced in the elevated plus-maze test, as compared with the control group (t=-3.584, P<0.05; t=-3.992, P<0.05. However, the total distance in the open field test showed no significant difference between the two groups (t=-0.96, P>0.05. Moreover, compared with the control group, the treatment group had significantly higher levels of serum ammonia (t=-3.168, P<0.05, ALT (t=4.316, P<0.05, AST (t=-2.581, P<0.05, and TBil (t=-9.127, P<0.01. ConclusionMice with AHE induced by an intraperitoneal injection of low-dose TAA have anxiety-related behaviors

  6. The hypertension drug, verapamil, activates Nrf2 by promoting p62-dependent autophagic Keap1 degradation and prevents acetaminophen-induced cytotoxicity.

    Science.gov (United States)

    Lee, Da Hyun; Park, Jeong Su; Lee, Yu Seol; Sung, Su Haeng; Lee, Yong-Ho; Bae, Soo Han

    2017-02-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) provides a cellular defense against oxidative stress by inducing the expression of antioxidant and detoxification enzymes. The calcium antagonist, verapamil, is an FDA-approved drug prescribed for the treatment of hypertension. Here, we show that verapamil acts as a potent Nrf2 activator without causing cytotoxicity, through degradation of Kelch-like ECH-associated protein 1 (Keap1), a Nrf2 repressor. Furthermore, verapamilinduced Keap1 degradation is prominently mediated by a p62-dependent autophagic pathway. Correspondingly, verapamil protects cells from acetaminophen-induced oxidative damage through Nrf2 activation. These results demonstrated the underlying mechanisms for the protective role of verapamil against acetaminophen-induced cytotoxicity. [BMB Reports 2017; 50(2): 91-96].

  7. Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in the Netherlands.

    NARCIS (Netherlands)

    Widdowson, MA; Jaspers, WJ; Poel, van der WH; Verschoor, F.; Husman, AM de Roda; Winter, HL; Zaaijer, H.L.; Koopmans, M

    2003-01-01

    Increasing evidence suggests that hepatitis E virus (HEV) infection may occur in developed countries and that swine may act as a reservoir. We report a cluster of 2 confirmed cases and 1 presumptive case of hepatitis associated with HEV. The typed strain from 1 case was related to HEV strains found

  8. Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in the Netherlands.

    NARCIS (Netherlands)

    Widdowson, MA; Jaspers, WJ; Poel, van der WH; Verschoor, F.; Husman, AM de Roda; Winter, HL; Zaaijer, H.L.; Koopmans, M

    2003-01-01

    Increasing evidence suggests that hepatitis E virus (HEV) infection may occur in developed countries and that swine may act as a reservoir. We report a cluster of 2 confirmed cases and 1 presumptive case of hepatitis associated with HEV. The typed strain from 1 case was related to HEV strains found

  9. A comparative study of regression of jaundice in patients of malaria and acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    D.K. Kochar, K. Kaswan, S.K. Kochar, P. Sirohi, M. Pala, A. Kochar , R.P. Agrawal , A. Das

    2006-09-01

    Full Text Available Background & objectives: Jaundice is one of the common manifestations of severe malaria in adults.The purpose of this study is to compare the pattern of clinical and biochemical parameters such asserum bilirubin and liver enzyme levels in patients of malaria with jaundice and acute viral hepatitis.Methodology: The present study was conducted on 34 patients of malaria with jaundice and 15patients of acute viral hepatitis. Estimation of serum bilirubin, aspartate amino transferase (AST,alanine amino transferase (ALT and alkaline phosphatase was done daily using standard proceduresin malaria patients and weekly in acute viral hepatitis patients.Results: Mean level of serum bilirubin on first day in malaria and acute viral hepatitis patients was7.07 ± 3.94 and 10.38 ± 7.87 mg%, whereas on Day 8 it was 1.19 ± 1.43 and 7.88 ± 7.02 mg%respectively. Mean level of AST on Day 1 in malaria and acute viral hepatitis patients was 158.47 ±120.35 and 1418.6 ± 834.11 IU/L, whereas on Day 8 it was 41 ± 28.33 and 775.3 ± 399.01IU/L respectively. Mean level of ALT on Day 1 in malaria and acute viral hepatitis patients was220.14 ± 145.61 and 1666.67 ± 1112.77 IU/L, whereas on Day 8 it was 50.85 ± 37.31 and 823.8 ±475.06 IU/L respectively. Mean level of serum alkaline phosphatase on Day 1 in malaria and acuteviral hepatitis patients was 394.74 ± 267.78 and 513.4 ± 324.7 IU/L, whereas on Day 8 it was84.76 ± 68.50 and 369.27 ± 207.75 IU/L respectively.Interpretation & conclusion: We observed that resolution of jaundice in malaria took 1–2 weeks incontrast 6 to 8 weeks in viral hepatitis. This difference in duration was statistically significant. Thus,jaundice not resolving in 1–2 weeks time in a patient of malaria requires serious consideration forpresence of other concomitant diseases including viral hepatitis.

  10. Acute Alcoholic Hepatitis | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available UK - MHRA A.2EudraCT number2006-004419-24 A.3Full title of the trial The Use of Sulfasalazine as an Anti-fibrotic in Acute...General Information on the Trial E.1 Medical condition or disease under investigation E.1.1Medical condition...(s) being investigated Acute Alcoholic Hepatitis MedDRA Classification E.1.2 Medical condition or disease un

  11. Different effects of selective β1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats.

    Science.gov (United States)

    Rofaeil, Remon R; Kamel, Maha Y; Abdelzaher, Walaa Y

    2017-04-01

    Acetaminophen (APAP) overdose is a common cause of acute liver failure, and beta-blockers are commonly used drugs in clinical practice. This study aimed to evaluate the effect of two different beta-blocker agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male Wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg/day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration. Also, nebivolol increased reduced glutathione (GSH) which was reduced with APAP administration. Moreover, immunohistochemical examination revealed that nebivolol treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced, as compared to APAP group. The protective effects of nebivolol were also verified histopathologically. On the other hand, as compared to APAP group, oral administration of atenolol (50 mg/kg) increased hepatic injury parameters but did not change hepatic NO, MDA, and GSH. In conclusion, this study revealed that nebivolol not atenolol is protective against APAP-induced hepatotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS expression. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  12. Clinical analysis of clinical feature of sporadic acute icteric hepatitis A and hepatitis E: A report of 335 cases

    Directory of Open Access Journals (Sweden)

    Peng ZHU

    2014-10-01

    Full Text Available Objective To investigate the clinical feature and outcome of patients with pre-existing chronic liver disease were co-infected with acute icteric hepatitis A or E. Methods 335 patients diagnosed with acute icteric hepatitis in Southwest Hospital were divided into hepatitis A (HA group (n=100 and hepatitis E (HE group (n=235. The clinical features (age, gender, season distribution, prodromal symptom and laboratory data were analyzed retrospectively. The stratification analysis was performed in the two groups according to the degree of hepatic fibrosis (APRI ratio index, HBV infection and cirrhosis status. The risk factors affecting the outcome were analyzed by logistic regression analysis. Results The mean age of patients of HE group (43.8±15.4 was older than that of HA group (32.0±13.0, P=8.045×10-11. Male patients were predominant in the two groups, and male/female ratio was higher in HE group (P=2.139×10-4. High prevalence was found within the period of February to April. Except for a higher total bilirubin (Tbil level (P<0.05 and lower incidence of fever, nausea and vomiting (P<0.05 in HE group, there was no difference in other clinical manifestations between the two groups. Compared with those without cirrhotic, cirrhosis patients co-infected with HA or HE showed an increased Tbil, decreased PTA and Alb, prolonged ALT and Tbil recovery time, higher incidence of hepatic decompensation and related complications, and higher mortality (P<0.05. Liver injury was more marked in patients with chronic liver disease who were infected with HAV or HEV with exacerbation of previous liver fibrosis. Alcohol consumption, age and chronic HBV infection were risk factors for liver decompensation in patients with cirrhosis associated with HE. Conclusion Sporadic acute icteric HA and HE showed similar clinical features, but different in age distribution and jaundice index. Its coexistence with HA or HE can cause severe liver decompensation, the

  13. Hemizygosity of transsulfuration genes confers increased vulnerability against acetaminophen-induced hepatotoxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hagiya, Yoshifumi; Kamata, Shotaro; Mitsuoka, Saya; Okada, Norihiko; Yoshida, Saori; Yamamoto, Junya; Ohkubo, Rika [Department of Biochemistry, Keio University School of Pharmaceutical Sciences, Tokyo 105-8512 (Japan); Abiko, Yumi [Environmental Biology Laboratory, School of Medicine, University of Tsukuba, Ibaraki 305-8575 (Japan); Yamada, Hidenori [Jobu Hospital for Respiratory Diseases, Maebashi 371-0048 (Japan); Akahoshi, Noriyuki [Department of Immunology, Akita University Graduate School of Medicine, Akita 010-8543 (Japan); Kasahara, Tadashi [Department of Biochemistry, Keio University School of Pharmaceutical Sciences, Tokyo 105-8512 (Japan); Kumagai, Yoshito [Environmental Biology Laboratory, School of Medicine, University of Tsukuba, Ibaraki 305-8575 (Japan); Ishii, Isao, E-mail: isao-ishii@umin.ac.jp [Department of Biochemistry, Keio University School of Pharmaceutical Sciences, Tokyo 105-8512 (Japan)

    2015-01-15

    The key mechanism for acetaminophen hepatotoxicity is cytochrome P450 (CYP)-dependent formation of N-acetyl-p-benzoquinone imine, a potent electrophile that forms protein adducts. Previous studies revealed the fundamental role of glutathione, which binds to and detoxifies N-acetyl-p-benzoquinone imine. Glutathione is synthesized from cysteine in the liver, and N-acetylcysteine is used as a sole antidote for acetaminophen poisoning. Here, we evaluated the potential roles of transsulfuration enzymes essential for cysteine biosynthesis, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), in acetaminophen hepatotoxicity using hemizygous (Cbs{sup +/−} or Cth{sup +/−}) and homozygous (Cth{sup −/−}) knockout mice. At 4 h after intraperitoneal acetaminophen injection, serum alanine aminotransferase levels were highly elevated in Cth{sup −/−} mice at 150 mg/kg dose, and also in Cbs{sup +/−} or Cth{sup +/−} mice at 250 mg/kg dose, which was associated with characteristic centrilobular hepatocyte oncosis. Hepatic glutathione was depleted while serum malondialdehyde accumulated in acetaminophen-injected Cth{sup −/−} mice but not wild-type mice, although glutamate–cysteine ligase (composed of catalytic [GCLC] and modifier [GCLM] subunits) became more activated in the livers of Cth{sup −/−} mice with lower K{sub m} values for Cys and Glu. Proteome analysis using fluorescent two-dimensional difference gel electrophoresis revealed 47 differentially expressed proteins after injection of 150 mg acetaminophen/kg into Cth{sup −/−} mice; the profiles were similar to 1000 mg acetaminophen/kg-treated wild-type mice. The prevalence of Cbs or Cth hemizygosity is estimated to be 1:200–300 population; therefore, the deletion or polymorphism of either transsulfuration gene may underlie idiosyncratic acetaminophen vulnerability along with the differences in Cyp, Gclc, and Gclm gene activities. - Highlights: • Cbs{sup +/−}, Cth{sup +/−}, and

  14. Acute sterol o-acyltransferase 2 (SOAT2 knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

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    Stephanie M Marshall

    Full Text Available The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE. We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2 increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD, the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

  15. Hepatitis A as an etiologic agent of acute liver failure in Latin America.

    Science.gov (United States)

    Ciocca, Mirta; Moreira-Silva, Sandra Fagundes; Alegría, Sylvia; Galoppo, Maria Cristina; Ruttiman, Ricardo; Porta, Gilda; Da Silvera, Themis Reverbel; Rubio, Pilar; Macias, Mercedes; Cervantes, Yolanda; Avila-Aguero, Maria Luisa; Clemens, Sue Anne Costa; Clemens, Ralf; Weil, John

    2007-08-01

    This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). HAV was the main etiologic agent of ALF in the population studied.

  16. Extracorporal hemodialysis with acute or decompensated chronical hepatic failure

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    Wasem, Jürgen

    2006-04-01

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

  17. Fatal acute hepatic failure in a family infected with the hepatitis A virus subgenotype IB: A case report.

    Science.gov (United States)

    Yoshida, Yuichi; Okada, Yohei; Suzuki, Akiko; Kakisaka, Keisuke; Miyamoto, Yasuhiro; Miyasaka, Akio; Takikawa, Yasuhiro; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2017-09-01

    Hepatitis A viral infection is a well-known cause of subclinical or acute self-limited hepatitis. Few cases of hepatitis A virus (HAV)-associated acute liver failure (ALF) have been reported in low HAV endemic countries annually. To investigate the possible factors that affected the severity of HAV infection, a family cluster infected with the HAV subgenotype IB strain, which is not common in Japan, was described. This family consisted of five members who all were infected with HAV. Four of the five patients hospitalized except for an asymptomatic patient. Two of the five patients, men in their 50s and 60s, developed ALF, and one patient died. Various host factors, including sex (male), age, and a high bilirubin level, may affect the outcomes. Based on viral factors, HAV RNA was higher in the fatal case compared with others, and it decreased within a short period of time. The similarity of the nucleotide sequences was 99.9% among the HAV isolates based on an entire genomic sequence. Deletions and/or insertions on the HAV protein-coding sequences that caused a frameshift were found in surviving cases but not in the fatal case. The rapid clearance of increased HAV and the absence of defective HAV might be closely associated with the onset of liver failure.

  18. Molecular epidemiology of acute hepatitis B in the Netherlands in 2004 : nationwide survey

    NARCIS (Netherlands)

    van Houdt, R; Bruisten, S M; Koedijk, F D H; Dukers, N H T M; Op de Coul, E L M; Mostert, M C; Niesters, H G M; Richardus, J H; de Man, R A; van Doornum, G J J; van den Hoek, J A R; Coutinho, R A; van de Laar, M J W; Boot, H J

    2007-01-01

    To gain insight into hepatitis B virus (HBV) transmission in the Netherlands, epidemiological data and sera were collected from reported cases of acute HBV infections in the Netherlands in 2004. Cases were classified according to mode of transmission. A fragment of the S-gene of HBV (648 bp) was amp

  19. [Acute hepatitis after use of a herbal preparation with greater celandine (Chelidonium majus)

    NARCIS (Netherlands)

    Crijns, A.P.G.; Smet, P.A.G.M. de; Heuvel, M. van den; Schot, B.W.; Haagsma, E.B.

    2002-01-01

    A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an alternative therapist due to a skin complaint. After the medication had been

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  1. 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....

  2. Acute drug induced hepatitis secondary to a weight loss product purchased over the internet

    Directory of Open Access Journals (Sweden)

    Cross Tim JS

    2007-06-01

    Full Text Available Abstract Background Many people now seek alternative methods of weight loss. The internet provides a readily available source of weight reduction products, the ingredients of which are often unclear. The authors describe a case of acute hepatitis in a 20 year old woman caused by such a product purchased over the internet. Case Presentation A 20-year old woman presented with a two day history of abdominal pain, vomiting and jaundice. There were no identifiable risk factors for chronic liver disease. Liver function tests demonstrated an acute hepatitis (aminoaspartate transaminase 1230 IU/L. A chronic liver disease screen was negative. The patient had started a weight loss product (Pro-Lean, purchased over the internet two weeks prior to presentation. The patient was treated conservatively, and improved. The sequence of events suggests an acute hepatitis caused by an herbal weight loss product. Conclusion This case report highlights the dangers of weight loss products available to the public over the internet, and the importance of asking specifically about alternative medicines in patients who present with an acute hepatitis.

  3. Boceprevir, peginterferon and ribavirin for acute hepatitis C in HIV infected patients

    NARCIS (Netherlands)

    Hullegie, Sebastiaan J.; Claassen, Mark A. A.; van den Berk, Guido E. L.; Van der Meer, Jan T. M.; Posthouwer, Dirk; Lauw, Fanny N.; Leyten, Eliane M. S.; Koopmans, Peter P.; Richter, Clemens; van Eeden, Arne; Bierman, Wouter F. W.; Newsum, Astrid M.; Arends, Joop E.; Rijnders, Bart J. A.

    2016-01-01

    Background & Aims: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men and generally treated with pegylated interferon-alpha (PegIFN) and ribavirin (RBV) during 24 weeks. The addition of a protease inhibitor could shorten therapy without loss of efficac

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  5. Clinical characteristics of acute hepatitis A outbreak in Taiwan, 2015-2016: observations from a tertiary medical center.

    Science.gov (United States)

    Chen, Nan-Yu; Liu, Zhuo-Hao; Shie, Shian-Sen; Chen, Tsung-Hsing; Wu, Ting-Shu

    2017-06-20

    Acute hepatitis A is a fecal-oral transmitted disease related to inadequate sanitary conditions. In addition to its traditional classification, several outbreaks in the men who have sex with men (MSM) population have resulted in acute hepatitis A being recognized as a sexually transmitted disease. However, few studies have clarified the clinical manifestations in these outbreaks involving the MSM population. Beginning in June 2015, there was an outbreak of acute hepatitis A involving the MSM population in Northern Taiwan. We conducted a 15-year retrospective study by recruiting 207 patients with the diagnosis of acute hepatitis A that included the pre-outbreak (January 2001 to May 2015) and outbreak (June 2015 to August 2016) periods in a tertiary medical center in Northern Taiwan. Using risk factors, comorbidities, presenting symptoms, laboratory test results and imaging data, we aimed to evaluate the clinical significance of acute hepatitis A in the MSM population, where human immunodeficiency virus (HIV) coinfection is common. There was a higher prevalence of reported MSM (p hepatitis A during the outbreak period. The outbreak population had more prominent systemic symptoms, was more icteric with a higher total bilirubin level (p hepatitis A relapse. The clinical course of acute hepatitis A during an outbreak involving the MSM and HIV-positive population is more symptomatic and protracted than in the general population.

  6. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    . Prospectively, serial measurements of serum phosphate were performed in 125 patients with severe acetaminophen poisoning. The optimum threshold value of serum phosphate to discriminate nonsurvivors was identified. Prognostic value and speed of identification were compared with those of the King's College...... after acetaminophen overdose is seen exclusively in nonsurvivors, which makes it a highly specific as well as sensitive predictor of nonsurvival. We propose that hyperphosphatemia is caused by renal dysfunction in the absence of hepatic regeneration, as the latter appears to be associated with lowering...

  7. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...

  8. Encephalitis, acute renal failure, and acute hepatitis triggered by a viral infection in an immunocompetent young adult: a case report

    Directory of Open Access Journals (Sweden)

    Khattab Mahmoud

    2009-11-01

    Full Text Available Abstract Introduction Cytomegalovirus generally causes self-limited, mild and asymptomatic infections in immunocompetent patients. An aggressive course in immunocompetent healthy patients is unusual. Case presentation We report the case of an immunocompetent 16-year-old Egyptian boy with encephalitis, acute renal failure, and acute hepatitis triggered by viral infection with a complete recovery following antiviral treatment. Conclusion We believe that this case adds to the understanding of the molecular biology, clinical presentation and increasing index of suspicion of many viral infections.

  9. OUTCOME OF ACUTE LIVER FAILURE DUE TO HEPATITIS A TREATED WITH MEDICAL MANAGEMENT

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    Thulaseedharan Nallaveettil

    2016-02-01

    Full Text Available BACKGROUND Acute liver failure is a heterogeneous entity and its prognosis varies with the aetiology. In India and other developing countries, hepatitis A virus is an important cause of acute liver failure. The prognostic factors and outcome of such patients should be studied separately. AIM OF THE STUDY To study the outcome of patients with acute liver failure due to hepatitis A treated with intensive supportive care and to determine the prognostic factors predicting the transplant free survival. MATERIALS AND METHODS In this observational study, all patients admitted in our hospital with ALF due to hepatitis A virus infection during the period of 3 years from January 1st 2013 to December 31st 2015 were selected; 40 patients satisfied the inclusion and exclusion criteria. Detailed history taking, physical examination, haematological and biochemical investigations were performed. The day-to-day progress and treatment given until discharge or death were recorded. RESULTS Overall mortality in acute liver failure due to hepatitis A was 30%. Transplant free survival was 100% in patients with grade I and II encephalopathy, 66.6% in grade III encephalopathy and 22.2% in grade IV encephalopathy (P less than 0.001. Extrahepatic manifestations were observed in 29 patients (72.5%, the most common was thrombocytopenia in 22 patients (55% followed by acute kidney injury in 12 patients (30%. CONCLUSIONS The grade of hepatic encephalopathy was the single most important factor that determined the prognosis. Patients with grade I and II encephalopathy had 100% spontaneous survival rate.

  10. First case report of an acute genotype 3 hepatitis E infected pregnant woman living in South-Eastern France.

    Science.gov (United States)

    Anty, R; Ollier, L; Péron, J M; Nicand, E; Cannavo, I; Bongain, A; Giordanengo, V; Tran, A

    2012-05-01

    In European countries, epidemiology of hepatitis E virus (HEV) infection is not well known. Although, seroprevalence of HEV Immunoglobulin G reached a few percent in European women, no acute hepatitis E during pregnancy has been described so far. Here, we report a case of an autochthonous HEV genotype 3 infection in a 41-years-old pregnant woman living in a non-endemic country. The acute hepatitis had a spontaneous good outcome for the mother and the child. In non-endemic areas where Hepatitis E infections are emerging, unexplained cytolysis, whatever its level, in a pregnant woman could be investigated for HEV, using biological molecular and serology tools.

  11. Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.

    Science.gov (United States)

    Lee, Jeonghun; Lee, Mi Sun; Nam, Kwan Woo

    2014-07-01

    Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.

  12. Acute interstitial nephritis with acetaminophen and alcohol intoxication

    Directory of Open Access Journals (Sweden)

    Alexopoulou Iakovina

    2011-04-01

    Full Text Available Abstract Drug-induced acute interstitial nephritis (AIN represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well established that acetaminophen metabolism, particularly at high doses, produces reactive metabolites that may induce renal and hepatic toxicity. It is also plausible however, that such reactive species could instead alter renal peptide immunogenicity, thereby inducing AIN. In the following report, we review a possible mechanism for the acetaminophen-induced AIN observed in our patient and also discuss the potential involvement of acute alcohol ingestion in disease onset. The objective of our report is to increase awareness of healthcare professionals to the potential involvement of these commonly used agents in AIN pathogenesis.

  13. Stent grafting of acute hepatic artery bleeding following pancreatic head resection

    Energy Technology Data Exchange (ETDEWEB)

    Stoupis, Christoforos [University of Berne, Inselspital, Department of Diagnostic, Interventional and Pediatric Radiology, Berne (Switzerland); Kreisspital, Radiology, Maennedorf (Switzerland); Ludwig, Karin; Triller, Juergen [University of Berne, Inselspital, Department of Diagnostic, Interventional and Pediatric Radiology, Berne (Switzerland); Inderbitzin, Daniel [University of Berne, Inselspital, Clinic for Visceral and Transplantation Surgery, Berne (Switzerland); Do, Dai-Do [University of Berne, Inselspital, Clinic for Angiology, Berne (Switzerland)

    2007-02-15

    The purpose of this study was to report the potential of hepatic artery stent grafting in cases of acute hemorrhage of the gastroduodenal artery stump following pancreatic head resection. Five consecutive male patients were treated because of acute, life-threatening massive bleeding. Instead of re-operation, emergency angiography, with the potential of endovascular treatment, was performed. Because of bleeding from the hepatic artery, a stent graft (with the over-the-wire or monorail technique) was implanted to control the hemmorhage by preserving patency of the artery. The outcome was evaluated. In all cases, the hepatic artery stent grafting was successfully performed, and the bleeding was immediately stopped. Clinically, immediately after the procedure, there was an obvious improvement in the general patient condition. There were no immediate procedure-related complications. Completion angiography (n=5) demonstrated control of the hemorrhage and patency of the hepatic artery and the stent graft. Although all patients recovered hemodynamically, three individuals died 2 to 10 days after the procedure. The remaining two patients survived, without the need for re-operation. Transluminal stent graft placement in the hepatic artery is a safe and technically feasible solution to control life-threatening bleeding of the gastroduodenal artery stump. (orig.)

  14. Acetaminophen-induced hepatotoxicity and protein nitration in neuronal nitric-oxide synthase knockout mice.

    Science.gov (United States)

    Agarwal, Rakhee; Hennings, Leah; Rafferty, Tonya M; Letzig, Lynda G; McCullough, Sandra; James, Laura P; MacMillan-Crow, Lee Ann; Hinson, Jack A

    2012-01-01

    In overdose acetaminophen (APAP) is hepatotoxic. Toxicity occurs by metabolism to N-acetyl-p-benzoquinone imine, which depletes GSH and covalently binds to proteins followed by protein nitration. Nitration can occur via the strong oxidant and nitrating agent peroxynitrite, formed from superoxide and nitric oxide (NO). In hepatocyte suspensions we reported that an inhibitor of neuronal nitric-oxide synthase (nNOS; NOS1), which has been reported to be in mitochondria, inhibited toxicity and protein nitration. We recently showed that manganese superoxide dismutase (MnSOD; SOD2) was nitrated and inactivated in APAP-treated mice. To understand the role of nNOS in APAP toxicity and MnSOD nitration, nNOS knockout (KO) and wild-type (WT) mice were administered APAP (300 mg/kg). In WT mice serum alanine aminotransferase (ALT) significantly increased at 6 and 8 h, and serum aspartate aminotransferase (AST) significantly increased at 4, 6 and 8 h; however, in KO mice neither ALT nor AST significantly increased until 8 h. There were no significant differences in hepatic GSH depletion, APAP protein binding, hydroxynonenal covalent binding, or histopathological assessment of toxicity. The activity of hepatic MnSOD was significantly lower at 1 to 2 h in WT mice and subsequently increased at 8 h. MnSOD activity was not altered at 0 to 6 h in KO mice but was significantly decreased at 8 h. There were significant increases in MnSOD nitration at 1 to 8 h in WT mice and 6 to 8 h in KO mice. Significantly more nitration occurred at 1 to 6 h in WT than in KO mice. MnSOD was the only observed nitrated protein after APAP treatment. These data indicate a role for nNOS with inactivation of MnSOD and ALT release during APAP toxicity.

  15. Saponins (Ginsenosides) from the Leaves of Panax quinquefolius Ameliorated Acetaminophen-Induced Hepatotoxicity in Mice.

    Science.gov (United States)

    Xu, Xing-Yue; Hu, Jun-Nan; Liu, Zhi; Zhang, Rui; He, Yu-Fang; Hou, Wei; Wang, Zhi-Qing; Yang, Ge; Li, Wei

    2017-05-10

    Acetaminophen (APAP) overdose is one of the most common inducements of drug-induced liver injury (DILI) in the world. The main purpose of this paper was to investigate the liver protection activity of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the involved mechanisms were demonstrated for the first time. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with 250 mg/kg APAP. Severe liver injury was exerted at 24 h post-APAP, and hepatotoxicity was assessed. Our results showed that pretreatment with PQS significantly decreased the serum alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β) levels in a dose-dependent manner as compared to the APAP administration. Meanwhile, compared with that in the APAP group, PQS decreased hepatic malondialdehyde (MDA) contents and 4-hydroxynonenal (4-HNE) expression and restored reduced glutathione (GSH) content and superoxide dismutase (SOD) activity in livers of mice. PQS inhibited the overexpression of pro-inflammatory factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the liver tissues. Furthermore, Western blotting analysis revealed that PQS pretreatment inhibited the activation of apoptotic signaling pathways via increase of Bcl-2 and decrease of Bax and caspase-3 protein expression levels. Liver histopathological observation provided further evidence that PQS pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration, and congestion. Biological indicators of nitrative stress such as 3-nitrotyrosine (3-NT) were inhibited after PQS pretreatment, compared to the APAP group. The present study clearly demonstrates that PQS exerts a protective effect against APAP-induced hepatic injury because of its antioxidant, anti-apoptotic, and anti-inflammatory activities. The findings from

  16. Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C.

    Science.gov (United States)

    Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

    2016-03-01

    Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

  17. [Acute non-A non-B viral hepatitis].

    Science.gov (United States)

    Findor, J A; Lafage, M; Bruch Igartua, E M; Domecq, P; Firpo, A M; Domecq, R B

    1980-01-01

    Thirty-one patients HBs Ag negative seen between january 1978 and june 1980 were studied. Twenty-four of them were males and seven females. Their age ranged between 13 and 58 years. All of them were anti-HAV IgM negative. Six patients presented simultaneously Anti HBc and Anti HBs in the two first weeks of the illness. This fact could be imputed to an acquired immunity due to a previous infection with virus B. None of the patients studied had evidence of infectious mononucleosis or cytomegalovirus. In view of the absence of the markers of recent infection due to virus A and B these patients were considered to have a non A non B hepatitis. Twelve patients had evidence of previous hepatitis, thirteen had acquired the infection by parenteral route; four were post-transfusional and in six cases there was an epidemic medium. Forty-five percent of the patients studied had a biphasic elevation of the aminotransferases, and twenty percent had a cholestatic form. Two of the patients turned into a chronic active hepatitis and another one died of submasive necrosis; in both cases the via of infection was parenteral.

  18. Effects of acute hepatic and renal failure on pharmacokinetics of flunixin meglumine in rats.

    Science.gov (United States)

    Hwang, Youn-Hwan; Yun, Hyo-In

    2011-01-01

    The aim of this study was to investigate the effects of hepatic and renal failure on the pharmacokinetics of flunixin in carbon tetrachloride (CCl(4))- and glycerol-treated rats. After intravenous administration of flunixin (2 mg/kg), the plasma concentration of flunixin was measured by high-performance liquid chromatography. Both acute hepatic and renal failure resulted in significantly increased area under the curve (AUC), prolonged elimination half-life (t(1/2β)), and reduced total body clearance (Cl(tot)) compared with respective controls (Pflunixin.

  19. Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization.

    Science.gov (United States)

    Yoo, Sun Hong; Jang, Jeong Won; Kwon, Jung Hyun; Jung, Seung Min; Jang, Bohyun; Choi, Jong Young

    2016-12-01

    Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. Our findings suggest that preemptive antiviral therapy significantly reduces the risk of

  20. Flow cytometry assay of myeloid dendritic cells (mDCs) in peripheral blood during acute hepatitis C: Possible pathogenetic mechanisms

    Institute of Scientific and Technical Information of China (English)

    Alessandro Perrella; Oreste Perrella; Luigi Atripaldi; Pasquale Bellopede; Tommaso Patarino; Costanza Sbreglia; Giovanni Tarantino; Paolo Sorrentino; Paolo Conca; Luca Ruggiero

    2006-01-01

    AIM: To asses the expression of myeloid dendritic cells (CD11c+) subset during acute HCV hepatitis and its possible involvement in natural history of the infection.METHODS: We enrolled 11 patients with acute hepatitis C (AHC) (Group A), 10 patients with acute hepatitis A (AHA) (as infective control-Group B) and 10 healthy donors (group C) in this study. All patients underwent selective flow cytometry gating strategies to assess the peripheral number of the myeloid dendritic cells (mDCs)to understand the possible role and differences during acute hepatitis.RESULTS: Eight of 11 patients with acute HCV hepatitis did not show any increase of mDCs compared to healthy individuals, while a significant decrease of mDCs was found in absolute cell count (z=-2.37; P<0.05) and percentage (z=-2.30; P<0.05) as compared with AHA.On the contrary, The remaining three patients of the group A had a higher mDCs number and percentage as occur in group B. Interestingly, after six months, those patients did not show any increase of mDCs subset were chronically infected. while the three subjects with an increase of peripheral mDCs, as in HAV acute infection,resolved the illness.CONCLUSION: The lack of increase of mDCs during acute hepatitis C might be an important factor involved in chronicization of the infection.

  1. Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice

    Directory of Open Access Journals (Sweden)

    Ivan Ćavar

    2011-12-01

    Full Text Available Prostanoids are lipid compounds that mediate a variety of physiological and pathological functions in almost all body tissues and organs. Thromboxane (TX A2 is a powerful inducer of platelet aggregation and vasoconstriction and it has ulcerogenic activity in the gastrointestinal tract. Overdose or chronic use of a high dose of acetaminophen (N-acetyl-paminophenol, APAP is a major cause of acute liver failure in the Western world. We investigated whether TXA2 plays a role in host response to toxic effect of APAP. CBA/H Zg mice of both sexes were intoxicated with a single lethal or high sublethal dose of APAP, which was administered to animals by oral gavage. The toxicity of APAP was determined by observing the survival of mice during 48 h, by measuring concentration of alanine-aminotransferase (ALT in plasma 20-22 h after APAP administration and by liver histology. The results have shown that anti-thromboxane (TX B2 antibodies (anti-TXB2 and a selective inhibitor of thromboxane (TX synthase, benzylimidazole (BZI, were significantly hepatoprotective, while a selective thromboxane receptor (TPR antagonist, daltroban, was slightly protective in this model of acute liver injury. A stabile metabolite of TXA2, TXB2, and a stabile agonist of TPR, U-46619, had no influence on APAP-induced liver damage. Our findings suggest that TXA2 has a pathogenic role in acute liver toxicity induced with APAP, which was highly abrogated by administration of anti-TXB2. According to our results, this protection is mediated, at least in part, through decreased production of TXB2 by liver fragments ex vivo.

  2. Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection

    Science.gov (United States)

    Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

    2016-01-01

    Abstract Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. Clinical findings: We report a case of acute-onset CIDP that was initially diagnosed as GBS. Diagnoses: A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. Interventions: After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. Outcomes: A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Conclusion: Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered. PMID:27930572

  3. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    Directory of Open Access Journals (Sweden)

    Luciano Rezende Vilela

    2015-01-01

    Full Text Available Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD, protects against cocaine toxicity. URB597 (1.0 mg/kg abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

  4. Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level.

    Science.gov (United States)

    Fakurazi, S; Hairuszah, I; Nanthini, U

    2008-08-01

    Initiation of acetaminophen (APAP) toxicities is believed to be promoted by oxidative stress during the event of overdosage. The aim of the present study was to evaluate the hepatoprotective action of Moringa oleifera Lam (MO), an Asian plant of high medicinal value, against a single high dose of APAP. Groups of five male Sprague-Dawley rats were pre-administered with MO (200 and 800 mg/kg) prior to a single dose of APAP (3g/kg body weight; p.o). Silymarin was used as an established hepatoprotective drug against APAP induced liver injury. The hepatoprotective activity of MO extract was observed following significant histopathological analysis and reduction of the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in groups pretreated with MO compared to those treated with APAP alone. Meanwhile, the level of glutathione (GSH) was found to be restored in MO-treated animals compared to the groups treated with APAP alone. These observations were comparable to the group pretreated with silymarin prior to APAP administration. Group that was treated with APAP alone exhibited high level of transaminases and ALP activities besides reduction in the GSH level. The histological hepatocellular deterioration was also evidenced. The results from the present study suggested that the leaves of MO can prevent hepatic injuries from APAP induced through preventing the decline of glutathione level.

  5. Protective effects of 2,4-dihydroxybenzophenone against acetaminophen-induced hepatotoxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Yue-Ying He; Bao-Xu Zhang; Feng-Lan Jia

    2011-01-01

    AIM: To examine the effects of 2,4-dihydroxybenzophenone (BP-1), a benzophenone derivative used as an ultraviolet light absorbent, on acetaminophen (APAP)- induced hepatotoxicity in C57BL/6J mice. METHODS: Mice were administered orally with BP-1 at doses of 200, 400 and 800 mg/kg body weight respectively every morning for 4 d before a hepatotoxic dose of APAP (350 mg/kg body weight) was given subcutaneously. Twenty four hours after APAP intoxication, the serum enzyme including serum alaine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were measured and liver histopathologic changes were examined. RESULTS: BP-1 administration dramatically reduced serum ALT, AST and LDH levels. Liver histopathological examination showed that BP-1 administration antagonized APAP-induced liver pathological damage in a dose-dependent manner. Further tests showed that APAP-induced hepatic lipid peroxidation was reduced significantly by BP-1 pretreatment, and glutathione depletion was ameliorated obviously. CONCLUSION: BP-1 can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity, and reduction of oxidative stress might be part of the protection mechanism.

  6. Reversal of acetaminophen induced subchronic hepatorenal injury by propolis extract in rats.

    Science.gov (United States)

    Bhadauria, Monika; Nirala, Satendra Kumar

    2009-01-01

    The ethanolic extract of propolis (200mg/kg, p.o.) was evaluated against acetaminophen (APAP; 20mg/kg, p.o.) induced subchronic hepatorenal injury in rats. Administration of APAP significantly increased the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase, bilirubin and serum proteins, whereas concomitantly decreased hemoglobin, blood sugar and albumin. Hepatorenal reduced glutathione and activities of superoxide dismutase and catalase, hepatic CYPs i.e., aniline hydroxylase and amidopyrine-N-demethylase were significantly decreased after APAP intoxication. Lipid peroxidation showed significant elevation in both organs significantly after APAP assault. Total proteins, glycogen contents and the activities of certain metabolic enzymes i.e., adenosine triphosphatase, alkaline phosphatase and acid phosphatase were altered after APAP administration. Propolis extract exhibited curative effects by reversing APAP induced alterations in blood biochemical variables, CYP enzymes and markers of oxidative stress. Histopathological analysis of liver and kidney was consistent with the biochemical findings and led us to conclude the curative potential of propolis against APAP induced hepatorenal injury. Copyright © 2008 Elsevier B.V. All rights reserved.

  7. Immune reconstitution inflammatory syndrome Kaposi sarcoma in the liver manifesting as acute obstructive hepatitis: another potential role for montelukast?

    Science.gov (United States)

    Read, P J; Lucas, S; Morris, S; Kulasegaram, R

    2013-02-01

    Immune reconstitution inflammatory syndrome has been described in Kaposi sarcoma, but does not usually manifest as acute hepatitis. We describe a case of rapid obstructive jaundice after initiation of antiretroviral therapy, in which the liver biopsy confirmed hepatic Kaposi sarcoma, and the clinical course was altered by the addition of montelukast.

  8. Ly6Chi Monocytes and Their Macrophage Descendants Regulate Neutrophil Function and Clearance in Acetaminophen-Induced Liver Injury

    Science.gov (United States)

    Graubardt, Nadine; Vugman, Milena; Mouhadeb, Odelia; Caliari, Gabriele; Pasmanik-Chor, Metsada; Reuveni, Debby; Zigmond, Ehud; Brazowski, Eli; David, Eyal; Chappell-Maor, Lousie; Jung, Steffen; Varol, Chen

    2017-01-01

    Monocyte-derived macrophages (MoMF) play a pivotal role in the resolution of acetaminophen-induced liver injury (AILI). Timely termination of neutrophil activity and their clearance are essential for liver regeneration following injury. Here, we show that infiltrating Ly6Chi monocytes, their macrophage descendants, and neutrophils spatially and temporally overlap in the centrilobular necrotic areas during the necroinflammatory and resolution phases of AILI. At the necroinflammatory phase, inducible ablation of circulating Ly6Chi monocytes resulted in reduced numbers and fractions of reactive oxygen species (ROS)-producing neutrophils. In alignment with this, neutrophils sorted from monocyte-deficient livers exhibited reduced expression of NADPH oxidase 2. Moreover, human CD14+ monocytes stimulated with lipopolysaccharide or hepatocyte apoptotic bodies directly induced ROS production by cocultured neutrophils. RNA-seq-based transcriptome profiling of neutrophils from Ly6Chi monocyte-deficient versus normal livers revealed 449 genes that were differentially expressed with at least twofold change (p ≤ 0.05). In the absence of Ly6Chi monocytes, neutrophils displayed gene expression alterations associated with decreased innate immune activity and increased cell survival. At the early resolution phase, Ly6Chi monocytes differentiated into ephemeral Ly6Clo MoMF and their absence resulted in significant accumulation of late apoptotic neutrophils. Further gene expression analysis revealed the induced expression of a specific repertoire of bridging molecules and receptors involved with apoptotic cell clearance during the transition from Ly6Chi monocytes to MoMF. Collectively, our findings establish a phase-dependent task division between liver-infiltrating Ly6Chi monocytes and their MoMF descendants with the former regulating innate immune functions and cell survival of neutrophils and the later neutrophil clearance. PMID:28620383

  9. [Acute hepatitis after use of a herbal preparation with greater celandine (Chelidonium majus)].

    Science.gov (United States)

    Crijns, A P G; de Smet, P A G M; van den Heuvel, M; Schot, B W; Haagsma, E B

    2002-01-19

    A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an alternative therapist due to a skin complaint. After the medication had been withdrawn, clinical recovery was rapid and the hepatic functions returned to normal within 2 months. The hepatitis was ascribed to the known hepatotoxic effects of C. majus. In view of the increasing popularity of herbal remedies, greater awareness of side effects, such as hepatotoxicity, is needed. Quite a number of herbal preparations carry the risk of liver damage. The supposed clinical effectiveness of herbal remedies does not seem to always outweigh the potential risks. In the event of non-clarified liver function disturbances the ingestion of supposedly harmless, but potentially hepatotoxic, herbal products should be considered.

  10. xCT deficiency aggravates acetaminophen-induced hepatotoxicity under inhibition of the transsulfuration pathway.

    Science.gov (United States)

    Kang, Eun Sil; Lee, Jaeyong; Homma, Takujiro; Kurahashi, Toshihiro; Kobayashi, Sho; Nabeshima, Atsunori; Yamada, Sohsuke; Seo, Han Geuk; Miyata, Satoshi; Sato, Hideyo; Fujii, Junichi

    2017-01-01

    Cystine, an oxidized form of cysteine (Cys), is imported into cells via the protein xCT, which is also associated with the export of glutamate as the counter amino acid. In the current study, we attempted to rationalize roles of xCT in the livers of male mice. While xCT was not expressed in the livers of ordinary mice, it was induced under conditions of glutathione depletion, caused by the administration of acetaminophen (AAP). To differentiate the role between xCT and the transsulfuration pathway on the supply of Cys, we employed an inhibitor of the enzyme cystathionine γ-lyase, propargylglycine (PPG). This inhibitor caused a marked aggravation in AAP-induced hepatic damage and the mortality of the xCT(-/-) mice was increased to a greater extent than that for the xCT(+/+) mice. While a PPG pretreatment had no effect on liver condition or Cys levels, the administration of AAP to the PPG-pretreated mice reduced the levels of Cys as well as glutathione to very low levels in both the xCT(+/+) and xCT(-/-) mice. These findings indicate that the transsulfuration pathway plays a major role in replenishing Cys when glutathione levels are low. Moreover, an ascorbic acid insufficiency, induced by Akr1a ablation, further aggravated the AAP-induced liver damage in the case of the xCT deficiency, indicating that glutathione and ascorbic acid function cooperatively in protecting the liver. In conclusion, while the transsulfuration pathway plays a primary role in supplying Cys to the redox system in the liver, xCT is induced in cases of emergencies, by compensating for Cys supply systems.

  11. Repression of acetaminophen-induced hepatotoxicity by a combination of celastrol and brilliant blue G.

    Science.gov (United States)

    Abdelaziz, Heba A; Shaker, Mohamed E; Hamed, Mohamed F; Gameil, Nariman M

    2017-06-05

    The sterile inflammatory response is an eminent contributor to acetaminophen (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of signaling events preceded the NLRP3-inflammasome activation, like the transcription factor NF-κB and the purinergic receptor P2X7, is still unclear and needs further elucidation. Here, we investigated the pharmacological inhibition of these upstream signaling molecules by celastrol and brilliant blue G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice. The results indicated that both celastrol and BBG pretreatments, especially when combined together, curbed APAP-induced hepatocellular injury (ALT, AST and LDH) and death (necrosis and apoptosis). The underlying mechanisms of protection of such combination against APAP-challenge were attributed to their efficient cooperation in: i) preventing the consumption of hepatic antioxidants (reduced glutathione and superoxide dismutase); ii) limiting the overproduction of lipid peroxidation aldehydes (malondialdehyde and 4-hydroxynonenal) and total nitrate/nitrite products; iii) attenuating the inflammatory cells accumulation in the liver, as evidenced by reducing the number of F4/80 positive cells/field in immunostaining and myeloperoxidase activity; iv) reversing the dysregulation in production of pro-inflammatory (TNF-α, IL-17A and IL-23) and anti-inflammatory (IL-10) cytokines; and v) enhancing the reparative capacity of injured hepatocytes, as demonstrated by increasing the percentage of PCNA positive hepatocytes per field of immunostaining. In conclusion, this murine study elicits a potential clinical applicability and therapeutic utility of celastrol and BBG combination in human cases of APAP-overdose hepatotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Protective effect of stiripentol on acetaminophen-induced hepatotoxicity in rat.

    Science.gov (United States)

    Tran, A; Tréluyer, J M; Rey, E; Barbet, J; Ferracci, G; d'Athis, P; Vincent, J; Pons, G

    2001-02-01

    Acetaminophen (APAP) is mainly eliminated at a therapeutic dose through glucuronidation and sulfatation and a small fraction is oxidized by cytochromes P450 (CYP) 2E1, 3A4, and 1A2 to N-acetyl-p-benzoquinone-imine (NAPQI), a highly reactive metabolite further conjugated with glutathione into APAP-GSH, and then metabolized to APAP-cystein and APAP-mercapturate excreted in urine. After APAP overdose, the glucuronidation and sulfatation pathways are saturated and the production of NAPQI increases, causing hepatic injury. Stiripentol (STP); (200 mg/kg), an anticonvulsant drug inhibitor of CYP1A2 and CYP3A4 in vivo in humans was tested against APAP-induced toxicity in rat in comparison with N-acetylcysteine (NAC; 100 mg/kg). The mortality rates 24 h after APAP overdose (2 x 500 mg/kg) were 63% (control), 38% (NAC), 0% (STP), and 4% (STP + NAC). The mean plasma transaminase concentrations 5 and 24 h after overdose were significantly higher in control than in STP and NAC groups. The percentage of rats without microscopic liver necrosis 5 h after APAP overdose was significantly higher in rats receiving STP (100%), NAC (83%), or STP + NAC (83%) than controls (42%). In another experiment, four similar groups were administered 50 mg/kg APAP. Plasma AUC(0-5 h) for APAP-GSH, APAP-cystein, and APAP-mercapturate as well as urine APAP-mercapturate mean amounts were significantly lower in STP animals than in the other groups. STP (200 mg/kg) inhibited NAPQI synthesis through CYP inhibition, thus preventing both liver necrosis and mortality in rats.

  13. Acute cholestatic hepatitis caused by amoxicillin/clavulanate

    Science.gov (United States)

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

    2013-01-01

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

  14. Hepatic artery stent-grafts for the emergency treatment of acute bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Bellemann, Nadine, E-mail: nadine.bellemann@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Sommer, Christof-Matthias; Mokry, Theresa; Kortes, Nikolas; Gnutzmann, Daniel; Gockner, Theresa; Schmitz, Anne [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Weitz, Jürgen [Department of Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Department for Visceral, Thoracic and Vascular Surgery at the University Hospital, Technical University Dresden (Germany); Kauczor, Hans-Ulrich; Radeleff, Boris; Stampfl, Ulrike [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany)

    2014-10-15

    Highlights: • We report our experiences with stent-grafts for the treatment of acute hemorrhage from the hepatic artery or the stump of the gastroduodenal artery. • The technical success of stent-graft implantation was 88%. • The bleeding ceased immediately after stent-graft implantation in 88%. • The complication rate was 21%. - Abstract: Purpose: We evaluated the technical success and clinical efficacy of stent-graft implantation for the emergency management of acute hepatic artery bleeding. Methods: Between January 2010 and July 2013, 24 patients with hemorrhage from the hepatic artery were scheduled for emergency implantation of balloon expandable stent-grafts. The primary study endpoints were technical and clinical success, which were defined as successful stent-graft implantation with sealing of the bleeding site at the end of the procedure, and cessation of clinical signs of hemorrhage. The secondary study endpoints were complications during the procedure or at follow-up and 30-day mortality rate. Results: In 23 patients, hemorrhage occurred after surgery, and in one patient hemorrhage occurred after trauma. Eight patients had sentinel bleeding. In most patients (n = 16), one stent-graft was implanted. In six patients, two overlapping stent-grafts were implanted. The stent-grafts had a target diameter between 4 mm and 7 mm. Overall technical success was 88%. The bleeding ceased after stent-graft implantation in 21 patients (88%). The mean follow-up was 137 ± 383 days. In two patients, re-bleeding from the hepatic artery occurred during follow-up after 4 and 29 days, respectively, which could be successfully treated by endovascular therapy. The complication rate was 21% (minor complication rate 4%, major complication rate 17%). The 30-day mortality rate was 21%. Conclusions: Implantation of stent-grafts in the hepatic artery is an effective emergency therapy and has a good technical success rate for patients with acute arterial hemorrhage.

  15. The Clinical Course of Cirrhosis Patients Hospitalized for Acute Hepatic Deterioration: A Prospective Bicentric Study.

    Science.gov (United States)

    Shi, Yu; Yan, Huadong; Zhou, Zhibo; Fang, Hong; Li, Jiawei; Ye, Honghua; Sun, Wenjie; Zhou, Wenhong; Ye, Jingfen; Yang, Qiao; Yang, Ying; Hu, Yaoren; Chen, Zhi; Sheng, Jifang

    2015-11-01

    Patients with cirrhosis are vulnerable to acute hepatic insults and are more likely to develop rapid hepatic deterioration. The aim of this study is to describe the clinical course of patients with cirrhosis and hospitalized for acute hepatic deterioration (AHD).This is a prospective study involving 163 patients with cirrhosis and AHD. The occurrence of organ failures, systemic inflammatory response syndrome (SIRS), and infections during hospital stay were recorded and the relationship between organ failure and death or SIRS/infection was subsequently analyzed.Of 163 patients, 35 did not develop any organ failure during in-hospital follow-ups (90-day mortality: 0%); 84 had intrahepatic organ failures (IH-OFs, defined by liver and/or coagulation failure) (90-day mortality: 22.0%); and 44 patients developed extra-hepatic organ failures (EH-OFs, defined by kidney, cerebral, circulation, and respiratory failure) on the basis of IH-OF with a 90-day mortality of 90.9%. On multivariable analysis by a Cox proportion hazard model, age, WBC, presence of IH-OF, and EH-OF all predicted 90-day death. A logistic regression analysis identified SIRS being associated with the development of EH-OF. Furthermore, IH-OF at admission and infections occurred during the hospital stay were shown to be another 2 potential risk factors.The clinical course of cirrhosis patients with acute hepatic injury was characterized by 3 consecutive stages (AHD, IH-OF, and EH-OF), which provided a clear risk stratification. The PIRO criteria provided an accurate frame for prognostication of those patients. The systemic inflammatory response syndrome may be a target for blocking the progression to the EH-OF stage.

  16. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

    Science.gov (United States)

    Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

    2015-07-01

    Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties.

  17. Clinical features of acute renal failure associated with hepatitis A virus infection.

    Science.gov (United States)

    Jung, Y J; Kim, W; Jeong, J B; Kim, B G; Lee, K L; Oh, K-H; Yoon, J-H; Lee, H-S; Kim, Y J

    2010-09-01

    Acute hepatitis A (AHA) is one of the most common infectious diseases; it is usually a self-limiting disease affecting the liver. Although extrahepatic manifestations are not common, some cases have been reported associated with acute renal failure. We reviewed the clinical features of patients with AHA complicated by acute renal failure (ARF group) and compared them with patients with noncomplicated AHA (non-ARF group). The medical records of 208 consecutive patients with AHA who were diagnosed between January 2003 and October 2008 were reviewed. We identified 15 patients (7.2%) with ARF associated with AHA. There were no differences between the ARF and non-ARF group with regard to gender and age. The peak value of alanine aminotransferase (ALT) (median: 6060 IU/L vs 1792 IU/L, P hepatic failure, and two patients died because of fulminant hepatic failure. There were no deaths among patients with noncomplicated AHA in the non-ARF group. Five patients underwent kidney biopsy; two patients were diagnosed with acute tubular necrosis, two patients with acute interstitial nephritis with IgA nephropathy and one patient with acute tubulointerstitial nephritis. All patients in the ARF group had microscopic haematuria and proteinuria (100%vs 31.1%, P < 0.001). Urine sodium levels were more than 10 mEq/L in 10 patients. The findings of high urinary sodium concentrations, microscopic haematuria and proteinuria did not support the diagnosis of hepatorenal syndrome (HRS). Patients with AHA with ARF had higher ALT levels, more prolonged PTs, and higher total bilirubin levels. The prognosis for these patients was poorer than for those without ARF. However, the patients with ARF and nonfulminant AHA had recovered with proper treatment and should not be confused with patients that have HRS.

  18. Chronic Elevation of Liver Enzymes in Acute Intermittent Porphyria Initially Misdiagnosed as Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    A. González Estrada

    2011-01-01

    Full Text Available Autoimmune hepatitis is a disease characterized by an elevation of liver enzymes, as well as specific autoantibodies. It is more common in women than men. We describe a 32-year-old woman with elevated transaminases, autoantibodies, and a liver biopsy result suggestive of autoimmune hepatitis. The indicated treatment was administered without showing a satisfactory response. The patient had a family history of acute intermittent porphyria (AIP so we decided to begin treatment with hematin, achieving a complete remission of the symptoms. Acute intermittent porphyria is a rare condition characterized by neurovisceral symptoms, abdominal pain being the most common of them. The disease has a higher prevalence among young women and certain European countries such as Sweden, Great Britain, and Spain. A correct diagnosis and prompt treatment are essential because patients affected by AIP must have a strict followup due to the fatal outcome of the outbreaks.

  19. Long-term ethanol exposure decreases the endotoxin-induced hepatic acute phase response in rats

    DEFF Research Database (Denmark)

    Glavind, Emilie; Vilstrup, Hendrik; Grønbaek, Henning

    2017-01-01

    -fed rats showed either no liver histopathological changes or varying degrees of steatosis. Ethanol feeding decreased the spontaneous liver mRNA expression of the prevailing acute phase protein alpha-2-macroglobulin by 30% (Ptumor necrosis factor...... an induced acute phase response is impaired in long-term ethanol-fed rats. METHODS: For six weeks, rats were either fed a Lieber-DeCarli ethanol-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low-dose of lipopolysaccharide...... (LPS) (0.5 mg/kg) to induce an acute phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute phase proteins. RESULTS: Ethanol...

  20. Acute risk for hepatitis E virus infection among HIV-1-positive pregnant women in central Africa

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    Caron Mélanie

    2012-10-01

    Full Text Available Abstract Background Hepatitis E virus (HEV, an enterically transmitted pathogen, is highly endemic in several African countries. Pregnant women are at particularly high risk for acute or severe hepatitis E. In Gabon, a central African country, the prevalence of antibodies to HEV among pregnant women is 14.1%. Recent studies have demonstrated unusual patterns of hepatitis E (chronic hepatitis, cirrhosis among immunodeficient patients. Findings We investigated the prevalence of antibodies to HEV among pregnant women infected with HIV-1 or HTLV-1 in Gabon. Of 243 samples collected, 183 were positive for HIV-1 and 60 for HTLV-1; 16 women (6.6% had IgG antibodies to HEV. The seroprevalence was higher among HIV-1-infected women (7.1% than HTLV-1-infected women (5.0%. Moreover, the HIV-1 viral load was significantly increased (p ≤ 0.02 among women with past-HEV exposure (1.3E+05 vs 5.7E+04 copies per ml, whereas no difference was found in HTLV-1 proviral load (9.0E+01 vs 1.1E+03 copies per ml. Conclusions These data provide evidence that HIV-1-infected women are at risk for acute or severe infection if they are exposed to HEV during pregnancy, with an increased viral load.

  1. Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A.

    Science.gov (United States)

    Cho, Hyosun; Kang, Hyojeung; Kim, Chang Wook; Kim, Hee Yeon; Jang, Jeong Won; Yoon, Seung Kew; Lee, Chang Don

    2016-03-01

    The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1 18.3% vs 3.7% vs 1.6%, respectively, pviral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.

  2. Acute Hepatitis after Ingestion of a Preparation of Chinese Skullcap and Black Catechu for Joint Pain

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    Charilaos Papafragkakis

    2016-01-01

    Full Text Available Many herbal preparations are routinely used and have been occasionally associated with a wide range of side effects, from mild to severe. Chinese skullcap and black catechu are herbal medications commonly used for their hepatoprotective and other properties. We report a case of acute toxic hepatitis associated with ingestion of Chinese skullcap and black catechu in one preparation for the alleviation of joint pain.

  3. Association between Plasma Fibrinogen Levels and Mortality in Acute-on-Chronic Hepatitis B Liver Failure

    OpenAIRE

    Zhexin Shao; Ying Zhao; Limin Feng; Guofang Feng; Juanwen Zhang; Jie Zhang

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patie...

  4. Enhanced Surveillance for Acute and Likely Acute Hepatitis B in Canada: 1999 to 2002

    Directory of Open Access Journals (Sweden)

    David Boulos

    2005-01-01

    Full Text Available OBJECTIVE: To assess the incidence of clinically identified hepatitis B cases, as well as the demographic and risk behaviour profiles of these cases in a defined Canadian population.

  5. Epidemiological characteristics and clinical manifestations of acute non-A-E hepatitis

    Directory of Open Access Journals (Sweden)

    Delić Dragan

    2010-01-01

    Full Text Available Background/Aim. Acute non-A, non-B, non-C, non-D, non-E hepatitis (non-A-E AH is an acute disease of the liver of unknown etiology for which one or more new, so far undetected, hepatotropic viruses may be responsible. The frequency of non-A-E AH ranges from 3.8% to 33.9%, and therefore it has a significant place within current infectology and hepatology. The aim of our study was to establish the frequency, clinical and biochemical characteristics, natural course and outcome of non-A-E AH and compare them with control groups affected by acute viral hepatitis A, B and C. Methods. This descriptive-analytic prospective study included 31 patients with non-A-E AH treated at the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade, from 2003 to 2008. They were followed up during the period not less than 6 months. The controls involved randomly selected patients, treated at the same time with a definite diagnosis of acute viral hepatitis A, B and C. Statistical data analysis used Mann-Whitney Utest, Student's t-test and variance analysis. The value of p < 0.05 was considered statistically significant. Results. The frequency of non-A-E AH was 7.6%. Almost no difference was found between sexes (male/female ratio was 1 : 1.07; it was developed in all age groups, with the highest incidence in the middle age (mean age was 38.32 ± 15.3 years. It appeared equally throughout the whole year. Out of risk factors, inoculation risk was predominant (before all, dental interventions, mostly involving urban population living in comfortable conditions. The duration of incubation varied much ranging from 20 to 180 days (median 60 days. By clinical course, moderate and icteric forms were most common, mostly corresponding to acute hepatitis A and C. On the other hand, by duration of the disease (mean duration was 67.1 ± 27.1 and chronic transformation, non-A-E AH resembled to acute hepatitis B. Progression to chronicity was recorded in 9

  6. Acute Right Ventricular Failure in a Patient with Hepatic Cirrhosis

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    Jose Soto Soto

    2012-01-01

    Full Text Available Pulmonary embolic disease is most commonly a manifestation of venous thromboembolism (VTE. However, fat, tumor, and air may all embolize to the pulmonary vasculature and lymphatics resulting in various clinical manifestations. Tumor emboli to small pulmonary vessels and lymphatics can lead to hypoxemic respiratory failure and shock. We present a 62-year-old male with history of mild COPD and end-stage liver disease secondary to hepatitis C admitted due to progressive shortness of breath and hypoxemia who developed shock and right ventricular failure. After a negative evaluation for venous thromboembolic disease, he had progressive respiratory and hemodynamic deterioration despite mechanical ventilation, renal replacement therapy, and vasopressive/inotropic support. Postmortem examination revealed diffuse micronodular moderately differentiated hepatocellular carcinoma (HCC without a discrete mass, as well as numerous HCC tumor emboli to the lung and focally to the heart, consistent with disseminated hepatocellular tumor microembolism.

  7. Metabolomics evaluation of the effects of green tea extract on acetaminophen-induced hepatotoxicity in mice.

    Science.gov (United States)

    Lu, Yihong; Sun, Jinchun; Petrova, Katya; Yang, Xi; Greenhaw, James; Salminen, William F; Beger, Richard D; Schnackenberg, Laura K

    2013-12-01

    Green tea has been purported to have beneficial health effects including protective effects against oxidative stress. Acetaminophen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. These studies explored the effects of green tea extract (GTE) on APAP-induced hepatotoxicity in liver tissue extracts using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance spectroscopy. Mice were orally administered GTE, APAP or GTE and APAP under three scenarios. APAP alone caused a high degree of hepatocyte necrosis associated with increases in serum transaminases and alterations in multiple metabolic pathways. The time of GTE oral administration relative to APAP either protected against or potentiated the APAP-induced hepatotoxicity. Dose dependent decreases in histopathology scores and serum transaminases were noted when GTE was administered prior to APAP; whereas, the opposite occurred when GTE was administered after APAP. Similarly, metabolites altered by APAP alone were less changed when GTE was given prior to APAP. Significantly altered pathways included fatty acid metabolism, glycerophospholipid metabolism, glutathione metabolism, and energy pathways. These studies demonstrate the complex interaction between GTE and APAP and the need to employ novel analytical strategies to understand the effects of dietary supplements on pharmaceutical compounds.

  8. Inhibition of Glycogen Synthase Kinase 3 Accelerated Liver Regeneration after Acetaminophen-Induced Hepatotoxicity in Mice.

    Science.gov (United States)

    Bhushan, Bharat; Poudel, Samikshya; Manley, Michael W; Roy, Nairita; Apte, Udayan

    2017-03-01

    Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of β-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice. Treatment with specific GSK3 inhibitor (L803-mts), starting from 4 hours after 600 mg/kg dose of APAP, resulted in early initiation of liver regeneration in a dose-dependent manner, without modifying the peak regenerative response. Acceleration of liver regeneration was not secondary to alteration of APAP-induced hepatotoxicity, which remained unchanged after GSK3 inhibition. Early cell cycle initiation in hepatocytes after GSK3 inhibition was because of rapid induction of cyclin D1 and phosphorylation of retinoblastoma protein. This was associated with increased activation of β-catenin signaling after GSK3 inhibition. Taken together, our study has revealed a novel role of GSK3 in liver regeneration after APAP overdose and identified GSK3 as a potential therapeutic target to improve liver regeneration after APAP-induced ALF. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Multiscale modeling reveals inhibitory and stimulatory effects of caffeine on acetaminophen-induced toxicity in humans.

    Science.gov (United States)

    Thiel, C; Cordes, H; Baier, V; Blank, L M; Kuepfer, L

    2017-02-01

    Acetaminophen (APAP) is a widely used analgesic drug that is frequently co-administered with caffeine (CAF) in the treatment of pain. It is well known that APAP may cause severe liver injury after an acute overdose. However, the understanding of whether and to what extent CAF inhibits or stimulates APAP-induced hepatotoxicity in humans is still lacking. Here, a multiscale analysis is presented that quantitatively models the pharmacodynamic (PD) response of APAP during co-medication with CAF. Therefore, drug-drug interaction (DDI) processes were integrated into physiologically based pharmacokinetic (PBPK) models at the organism level, whereas drug-specific PD response data were contextualized at the cellular level. The results provide new insights into the inhibitory and stimulatory effects of CAF on APAP-induced hepatotoxicity for crucially affected key cellular processes and individual genes at the patient level. This study might facilitate the risk assessment of drug combination therapies in humans and thus may improve patient safety in clinical practice. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  10. Hepatitis C and recurrent treatment-resistant acute ischemic stroke

    OpenAIRE

    Saxsena, Aneeta; Tarsia, Joseph; Dunn, Casey; Aysenne, Aimee; Shah, Basil; Moore, David F.

    2013-01-01

    Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such...

  11. Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans

    Science.gov (United States)

    Xiao, Changting; Pavlic, Mirjana; Szeto, Linda; Patterson, Bruce W.; Lewis, Gary F.

    2011-01-01

    OBJECTIVE The metabolism of hepatic- and intestinally derived lipoproteins is regulated in a complex fashion by nutrients, hormones, and neurologic and other factors. Recent studies in animal models suggest an important role for glucagon acting via the glucagon receptor in regulating hepatic triglyceride (TG) secretion. Here we examined the direct effects of glucagon on regulation of hepatic and intestinal lipoprotein metabolism in humans. RESEARCH DESIGN AND METHODS Eight healthy men underwent two studies each, in random order, 4–6 weeks apart in which de novo lipogenesis, kinetics of larger VLDL1 TG, and kinetics of VLDL1 and smaller VLDL2 apolipoprotein (apo)B100 and B48 were studied using established stable isotope enrichment methods. Subjects were studied in the constant fed state under conditions of a pancreatic clamp (with infusion of somatostatin, insulin, and growth hormone) at either basal glucagon (BG study, 64.5 ± 2.1 pg/mL) or hyperglucagonemia (high glucagon [HG] study, 183.2 ± 5.1 pg/mL). RESULTS There were no significant differences in plasma concentration of VLDL1 or VLDL2 TG, apoB100 or apoB48 between BG and HG studies. There was, however, lower (P lipoprotein metabolism. CONCLUSIONS Glucagon acutely regulates hepatic but not intestinal lipoprotein particle metabolism in humans both by decreasing hepatic lipoprotein particle production as well as by inhibiting particle clearance, with no net effect on particle concentration. PMID:20980459

  12. Bone marrow and nonbone marrow Toll like receptor 4 regulate acute hepatic injury induced by endotoxemia.

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    Edith Hochhauser

    Full Text Available BACKGROUND: Toll-like receptors (TLRs are expressed in immune cells and hepatocytes. We examined whether hepatic Toll-like receptor 4 (TLR4 is involved in the acute hepatic injury caused by the administration of lipopolysaccharide (LPS (septic shock model. METHODS: Wild type (WT, TLR4-deficient and chimera mice underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the liver or in the immune-hematopoietic system. Mice were injected with LPS and sacrificed 4 hours later. RESULTS: Compared to TLR4 deficient mice, WT mice challenged with LPS displayed increased serum liver enzymes and hepatic cellular inflammatory infiltrate together with increased serum and hepatic levels of interleukin 1β (IL-1β, tumor necrosis factor α (TNFα ,Up-regulation of hepatic mRNA encoding TLR4, IκB and c-jun expressions. TLR4 mutant mice transplanted with WT bone marrow were more protected than WT chimeric mice bearing TLR4 mutant hemopoietic cells from LPS, as seen by IL-1β and TNFα levels. We then used hepatocytes (Huh7 and macrophages from monocytic cell lines to detect TLR mRNA expression. Macrophages expressed a significantly higher level of TLR4 mRNA and TLR2 (more than 3000- and 8000-fold respectively compared with the hepatocyte cell line. LPS administration induced TLR4 activation in a hepatocyte cell line in a dose dependent manner while TLR2 mRNA hardly changed. CONCLUSIONS: These results suggest that TLR4 activation of hepatocytes participate in the immediate response to LPS induced hepatic injury. However, in this response, the contribution of TLR4 on bone marrow derived cells is more significant than those of the hepatocytes. The absence of the TLR4 gene plays a pivotal role in reducing hepatic LPS induced injury.

  13. Comparison of electronic laboratory reports, administrative claims, and electronic health record data for acute viral hepatitis surveillance.

    Science.gov (United States)

    Allen-Dicker, Joshua; Klompas, Michael

    2012-01-01

    Public health surveillance systems for acute hepatitis are limited: clinician reporting is insensitive and electronic laboratory reporting is nonspecific. Insurance claims and electronic health records are potential alternative sources. To compare the utility of laboratory data, diagnosis codes, and electronic health record combination data (current and prior viral hepatitis studies, liver function tests, and diagnosis codes) for acute hepatitis A and B surveillance. Retrospective chart review. Massachusetts ambulatory practice serving 350 000 patients per year. All patients seen between 1990 and 2008. Sensitivity and positive predictive value of immunoglobulin M (IgM), International Classification of Disease-Ninth Revision (ICD-9) diagnosis codes, and combination electronic health record data for acute hepatitis A and B. During the study period, there were 111 patients with positive hepatitis A IgMs, 154 with acute hepatitis A ICD-9 codes, and 77 with positive IgM and elevated liver function tests. On review, 79 cases were confirmed. Sensitivity and positive predictive value were 100% and 71% (95% confidence interval, 62%-79%) for IgM, 94% (92%-100%) and 48% (40%-56%) for ICD-9 codes and 97% (92%-100%) and 100% (96%-100%) for combination electronic health record data. There were 14 patients with positive hepatitis B core IgMs, 2564 with acute hepatitis B ICD-9 codes, and 125 with suggestive combinations of electronic health record data. Acute hepatitis B was confirmed in 122 patients. Sensitivity and positive predictive value were 9.4% (5.2%-16%) and 86% (60%-98%) for hepatitis B core IgM, 73% (65%-80%) and 3.6% (2.9%-4.4%) for ICD-9 codes, and 96% (91%-99%) and 98% (94%-99%) for electronic health record data. Laboratory surveillance using IgM tests overestimates the burden of acute hepatitis A and underestimates the burden of acute hepatitis B. Claims data are subject to many false positives. Electronic health record data are both sensitive and predictive

  14. Hepatitis E virus infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil

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    Nara Rubia de Freitas

    Full Text Available Hepatitis E virus (HEV infection has a worldwide distribution and represents an important cause of acute hepatitis. This study aims to investigate the occurrence of HEV infection and factors associated with this infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil. From April 2012 to October 2014, a cross-sectional study was conducted among 379 patients with acute non-A, non-B, non-C hepatitis in the City of Goiania, Central Brazil. Serum samples of all patients were tested for serological markers of HEV infection (anti-HEV IgM and IgG by ELISA. Positive samples were confirmed using immunoblot test. Anti-HEV IgM and IgG positive samples were tested for HEV RNA. Of the 379 serum samples, one (0.3% and 20 (5.3% were positive for anti-HEV IgM and IgG, respectively. HEV RNA was not found in any sample positive for IgM and/or IgG anti-HEV. After multivariate analysis, low education level was independently associated with HEV seropositivity (p = 0.005, as well as living in rural area, with a borderline p-value (p = 0.056. In conclusion, HEV may be responsible for sporadic self-limited cases of acute hepatitis in Central Brazil.

  15. Hepatitis E virus infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil

    Science.gov (United States)

    de Freitas, Nara Rubia; de Santana, Edna Braz Rocha; Silva, Ágabo Macedo da Costa e; da Silva, Sueli Meira; Teles, Sheila Araújo; Gardinali, Noemi Rovaris; Pinto, Marcelo Alves; Martins, Regina Maria Bringel

    2016-01-01

    Hepatitis E virus (HEV) infection has a worldwide distribution and represents an important cause of acute hepatitis. This study aims to investigate the occurrence of HEV infection and factors associated with this infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil. From April 2012 to October 2014, a cross-sectional study was conducted among 379 patients with acute non-A, non-B, non-C hepatitis in the City of Goiania, Central Brazil. Serum samples of all patients were tested for serological markers of HEV infection (anti-HEV IgM and IgG) by ELISA. Positive samples were confirmed using immunoblot test. Anti-HEV IgM and IgG positive samples were tested for HEV RNA. Of the 379 serum samples, one (0.3%) and 20 (5.3%) were positive for anti-HEV IgM and IgG, respectively. HEV RNA was not found in any sample positive for IgM and/or IgG anti-HEV. After multivariate analysis, low education level was independently associated with HEV seropositivity (p = 0.005), as well as living in rural area, with a borderline p-value (p = 0.056). In conclusion, HEV may be responsible for sporadic self-limited cases of acute hepatitis in Central Brazil. PMID:27759769

  16. Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy.

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    Rekha Gautam

    Full Text Available Acetaminophen is a widely prescribed drug used to relieve pain and fever; however, it is a leading cause of drug-induced liver injury and a burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing of acetaminophen was investigated using liver and sera samples with Fourier Transform Infrared microspectroscopy. The infrared spectra of acetaminophen treated livers in BALB/c mice show decrease in glycogen, increase in amounts of cholesteryl esters and DNA respectively. Rescue experiments using L-methionine demonstrate that depletion in glycogen and increase in DNA are abrogated with pre-treatment, but not post-treatment, with L-methionine. This indicates that changes in glycogen and DNA are more sensitive to the rapid depletion of glutathione. Importantly, analysis of sera identified lowering of glycogen and increase in DNA and chlolesteryl esters earlier than increase in alanine aminotransferase, which is routinely used to diagnose liver damage. In addition, these changes are also observed in C57BL/6 and Nos2(-/- mice. There is no difference in the kinetics of expression of these three molecules in both strains of mice, the extent of damage is similar and corroborated with ALT and histological analysis. Quantification of cytokines in sera showed increase upon APAP treatment. Although the levels of Tnfα and Ifnγ in sera are not significantly affected, Nos2(-/- mice display lower Il6 but higher Il10 levels during this acute model of hepatotoxicity. Overall, this study reinforces the growing potential of Fourier Transform Infrared microspectroscopy as a fast, highly sensitive and label-free technique for non-invasive diagnosis of liver damage. The combination of Fourier Transform Infrared microspectroscopy and cytokine analysis is a powerful tool to identify multiple biomarkers, understand differential host responses and evaluate therapeutic regimens during liver damage and, possibly, other diseases.

  17. Hepatitis B and Hepatitis C in Pregnancy

    Science.gov (United States)

    ... and hepatitis C infections during pregnancy? • How is hepatitis B virus infection spread? • What is acute hepatitis B virus infection? • What is chronic hepatitis B virus infection? • Can ...

  18. Hepatic perfusion changes in an experimental model of acute pancreatitis: Evaluation by perfusion CT

    Energy Technology Data Exchange (ETDEWEB)

    Tutcu, Semra [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Serter, Selim, E-mail: serterselim@gmail.co [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Kaya, Yavuz; Kara, Eray [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Nese, Nalan [Department of Pathology, Celal Bayar University, School of Medicine, Manisa (Turkey); Pekindil, Goekhan [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Coskun, Teoman [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey)

    2010-08-15

    Purpose: It is known that acute pancreatitis may cause secondary changes in several organs. Liver is one of these involved organs. In different experimental studies hepatic damages were shown histopathologically in acute pancreatitis but there are a few studies about perfusion disorders that accompany these histopathologic changes. Perfusion CT (pCT) provides the ability to detect regional and global alterations in organ blood flow. The purpose of the study was to describe hepatic perfusion changes in experimental acute pancreatitis model with pCT. Materials and methods: Forty Sprague-Dawley rats of both genders with average weights of 250 g were used. Rats were randomized into two groups. Twenty rats were in control group and 20 in acute pancreatitis group. pCT was performed. Perfusion maps were formed by processing the obtained images with perfusion CT software. Blood flow (BF) and blood volume (BV) values were obtained from these maps. All pancreatic and liver tissues were taken off with laparotomy and histopathologic investigation was performed. Student's t test was used for statistical analyses. Results: In pCT we found statistically significant increase in blood volume in both lobes of liver and in blood flow in right lobe of the liver (p < 0.01). Although blood flow in left lobe of the liver increased, it did not reach statistical significance. Conclusion: The quantitative analysis of liver parenchyma with pCT showed that acute pancreatitis causes a significant perfusion changes in the hepatic tissue. Systemic mediators seem to be effective as well as local inflammatory changes in perfusion changes.

  19. 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.

  20. Hepatic damage during acute pancreatitis in the rat

    Directory of Open Access Journals (Sweden)

    A.M.M. Coelho

    1997-08-01

    Full Text Available We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I and to five other groups corresponding to 2, 4, 12, 24 and 48 h after the induction of acute pancreatitis by the injection of 5% sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4 and in the presence of ADP (activated respiration, state 3. Serum amylase, transaminases (ALT and AST and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4 h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h there was an increase in state 4 respiration (45.65 ± 1.79 vs 28.96 ± 1.50 and a decrease in respiration control rate (3.53 ± 0.09 vs 4.45 ± 0.08 and in the ADP/O ratio (1.77 ± 0.02 vs 1.91 ± 0.01 compared to controls (P<0.05. These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min showed that arterial blood pressure remained normal up to 24 h (111 ± 3 mmHg while a significant decrease occurred in the 48-h group (91 ± 4 mmHg. These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an initial uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related

  1. 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

  2. PREVALENCE OF DIFFERENT VIRAL MARKERS IN PATIENTS OF ACUTE VIRAL HEPATITIS IN AND AROUND VISAKHAPATNAM : HOSPITAL BASED STUDY

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    Aruna Sree

    2015-04-01

    Full Text Available Acute viral hepatitis (AVH is a major public health problem and is an important cause of morbidity and mortality in the developing countries. AIM: The aim of the present study is to study the serological profile of acute viral hepatitis in children and adults admitted in King George Hospital, Visakhapatnam and also age and sex distribution of patients suffering from acute viral hepatitis and also comparing the etiological profile by studying serological markers of common viral agents. SUBJECTS AND METHODS: Samples were collected from 80 individuals with jaundice and other clinical and biochemical evidences of acute viral hepatitis . They were tested for hepatitis surface antigen, HBcIgM, HAVIgM, HEVIgM, Antibodies to HCV by the enzyme - linked immuno sorbent assay. RESULTS: Out of the 80 viral hepatitis cases (47 adults+33 children. In adults 20(42.5% patients presented HBV (26.96% was identified as the most common cause of acute hepatitis followed by HEV14 (29.8%, HEV+HAV4 (8.5% and HAV 6(12.76%. Co - infections with more than one virus were present in 5cases; HAV - HEV co - infection being the most common. In children 16(48.5% presented with HAV, HAV+HEV11 (33.3%, HEV4 (12.12%, HBV1 (3.03% CONCLUSIONS: Vaccination of adults against hepatitis B is indicated, along with sexual education to decrease the incidence of hepatitis which is found as common etiological agent in adults. The incidence of HAV and HEV in children shows that there is need for improvement in sanitation and food habits.

  3. Acute overactive endocannabinoid signaling induces glucose intolerance, hepatic steatosis, and novel cannabinoid receptor 1 responsive genes.

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    Maxwell A Ruby

    Full Text Available Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1. Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP, perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251 and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control, IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2, which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50% the majority (303 of 533 of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and

  4. Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan.

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    Ohnishi, Sachiyo; Kang, Jong-Hon; Maekubo, Hiroshi; Arakawa, Tomohiro; Karino, Yoshiyasu; Toyota, Joji; Takahashi, Kazuaki; Mishiro, Shunji

    2006-12-01

    In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.

  5. Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013.

    Science.gov (United States)

    Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Kobayashi, Tominari; Nagashima, Shigeo; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2016-04-01

    Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.

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

    Science.gov (United States)

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

    2015-09-01

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

  7. Risk factors and molecular characterization of acute sporadic symptomatic hepatitis E virus infection in Thailand

    Institute of Scientific and Technical Information of China (English)

    Kittiyod Poovorawan; Salyavit Jitmitrapab; Sombat Treeprasertsuk; Thanunrat Thongmee; Apiradee Theamboonlers; Pisit Tangkijvanich; Piyawat Komolmit; Yong Poovorawan

    2014-01-01

    Objective:To report clinical outcomes and viral genotypes of acute symptomatic hepatitis E virus (HEV) infection inThailand.Methods:Forty patients with acute symptomaticHEV infection were recruited during2009-2013.Clinical, demographic and laboratory data were collected.Diagnosis was accomplished by detection of anti-HEVIgM and/orHEVRNA in the serum or stool.HEV genotypes were classified by direct sequencing ofRT-PCRproducts and phylogenetic analysis. Results:The high risk group, comprising immune-compromised, liver cirrhosis and very elderly (>80 years) patients(17 cases), had higher levels of serum alkaline phosphatase at presentation compared with the low risk group.Two fatal cases resulted from acute hepatitisE in the high risk group.Initial clinical presentation did not show statistically significant differences.In six cases (6/40), the virus could be detected in serum or stool byRT-PCR and sequencing.Upon molecular characterization, the viruses were classified asHEV genotype3f and were in the same cluster as Thai swineHEV.Conclusions:Our data showed that acuteHEV infection has various clinical presentations and outcomes.Higher levels of serum alkaline phosphatase were observed in high risk patients.All isolated viruses were identified asHEV genotype3f possibly originating from swine.

  8. Iridoid Glycosides Fraction Isolated from Veronica ciliata Fisch. Protects against Acetaminophen-Induced Liver Injury in Mice

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    Shancai Tan

    2017-01-01

    Full Text Available Veronica ciliata Fisch. has traditionally been used in Tibetan medicine for the treatment of hepatitis, cholecystitis, rheumatism, and urticaria. We analyzed the chemical composition of the iridoid glycosides fraction (IGF isolated from V. ciliata and evaluated the antioxidant and hepatoprotective properties. The IGF was separated by high-speed countercurrent chromatography (HSCCC and the main compounds were identified by ultra-performance liquid chromatography coupled to a photodiode array. We determined the in vitro antioxidant ability of the IGF through radical scavenging assays and assessed the in vivo hepatoprotective potential in an acetaminophen- (APAP- induced acute liver injury murine model. The IGF was separated by HSCCC and three major iridoid glycosides (verproside, catalposide, and amphicoside were identified as potent antioxidants and hepatoprotective compounds. Treatment with the IGF significantly suppressed the APAP-induced elevation in serum alanine aminotransferase, aspartate aminotransferase, and tumor necrosis factor-alpha (TNF-α; improved serum total antioxidant capacity; decreased malondialdehyde formation; elevated superoxide dismutase and glutathione activity; and decreased expression of proinflammatory factors (TNF-α, nuclear factor kappa B in the liver. Finally, we examined the histopathology of resected livers for evidence of hepatoprotection. The protection conferred by the IGF may be related to the reinforcement of antioxidant defense systems.

  9. Iridoid Glycosides Fraction Isolated from Veronica ciliata Fisch. Protects against Acetaminophen-Induced Liver Injury in Mice

    Science.gov (United States)

    Tan, Shancai; Lu, Qiuxia; Shu, Yueyue; Sun, Yiran

    2017-01-01

    Veronica ciliata Fisch. has traditionally been used in Tibetan medicine for the treatment of hepatitis, cholecystitis, rheumatism, and urticaria. We analyzed the chemical composition of the iridoid glycosides fraction (IGF) isolated from V. ciliata and evaluated the antioxidant and hepatoprotective properties. The IGF was separated by high-speed countercurrent chromatography (HSCCC) and the main compounds were identified by ultra-performance liquid chromatography coupled to a photodiode array. We determined the in vitro antioxidant ability of the IGF through radical scavenging assays and assessed the in vivo hepatoprotective potential in an acetaminophen- (APAP-) induced acute liver injury murine model. The IGF was separated by HSCCC and three major iridoid glycosides (verproside, catalposide, and amphicoside) were identified as potent antioxidants and hepatoprotective compounds. Treatment with the IGF significantly suppressed the APAP-induced elevation in serum alanine aminotransferase, aspartate aminotransferase, and tumor necrosis factor-alpha (TNF-α); improved serum total antioxidant capacity; decreased malondialdehyde formation; elevated superoxide dismutase and glutathione activity; and decreased expression of proinflammatory factors (TNF-α, nuclear factor kappa B) in the liver. Finally, we examined the histopathology of resected livers for evidence of hepatoprotection. The protection conferred by the IGF may be related to the reinforcement of antioxidant defense systems. PMID:28293265

  10. Differential Gene Expression Profiles in Acute Hepatic Failure Model in Mice Infected with MHV-3 Virus Intervened by Anti-hepatic Failure Compound

    Institute of Scientific and Technical Information of China (English)

    HUANG Jiaquan; XIAO Fei; YU Haijing; HUANG Tiejun; HUANG Haiyan; NING Qin

    2007-01-01

    Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure in- fected with MHV-3 virus intervened by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% re- spectively 48 h after intrapefitoneal injection of MHV-3 (P<0.05). Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oli- gonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fg12, IL-8, IL-6, IFN-γ, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

  11. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models

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    Judit Pomothy

    2016-01-01

    Full Text Available Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1 were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21±26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6±14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.. No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.

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

    Science.gov (United States)

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

    2015-08-28

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

  13. 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.

  14. Case control study to identify risk factors for acute hepatitis C virus infection in Egypt

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    Kandeel Amr M

    2012-11-01

    Full Text Available Abstract Background Identification of risk factors of acute hepatitis C virus (HCV infection in Egypt is crucial to develop appropriate prevention strategies. Methods We conducted a case–control study, June 2007-September 2008, to investigate risk factors for acute HCV infection in Egypt among 86 patients and 287 age and gender matched controls identified in two infectious disease hospitals in Cairo and Alexandria. Case-patients were defined as: any patient with symptoms of acute hepatitis; lab tested positive for HCV antibodies and negative for HBsAg, HBc IgM, HAV IgM; and 7-fold increase in the upper limit of transaminase levels. Controls were selected from patients’ visitors with negative viral hepatitis markers. Subjects were interviewed about previous exposures within six months, including community-acquired and health-care associated practices. Results Case-patients were more likely than controls to have received injection with a reused syringe (OR=23.1, CI 4.7-153, to have been in prison (OR=21.5, CI 2.5-479.6, to have received IV fluids in a hospital (OR=13.8, CI 5.3-37.2, to have been an IV drug user (OR=12.1, CI 4.6-33.1, to have had minimal surgical procedures (OR=9.7, CI 4.2-22.4, to have received IV fluid as an outpatient (OR=8, CI 4–16.2, or to have been admitted to hospital (OR=7.9, CI 4.2-15 within the last 6 months. Multivariate analysis indicated that unsafe health facility practices are the main risk factors associated with transmission of HCV infection in Egypt. Conclusion In Egypt, focusing acute HCV prevention measures on health-care settings would have a beneficial impact.

  15. Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

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    B. Relja

    2012-01-01

    Full Text Available Acute ethanol intoxication increases the production of reactive oxygen species (ROS. Hemorrhagic shock with subsequent resuscitation (H/R also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.. Then, rats were hemorrhaged to a mean arterial blood pressure of 30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.. Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE and nitrosative (3-nitrotyrosine, 3-NT stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

  16. Inhibition of Hepatitis C Virus-Like Particle Binding to Target Cells by Antiviral Antibodies in Acute and Chronic Hepatitis C

    Science.gov (United States)

    Steinmann, Daniel; Barth, Heidi; Gissler, Bettina; Schürmann, Peter; Adah, Mohammed I.; Gerlach, J. Tilman; Pape, Gerd R.; Depla, Erik; Jacobs, Dirk; Maertens, Geert; Patel, Arvind H.; Inchauspé, Geneviève; Liang, T. Jake; Blum, Hubert E.; Baumert, Thomas F.

    2004-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis worldwide. The study of antibody-mediated virus neutralization has been hampered by the lack of an efficient and high-throughput cell culture system for the study of virus neutralization. The HCV structural proteins have been shown to assemble into noninfectious HCV-like particles (HCV-LPs). Similar to serum-derived virions, HCV-LPs bind and enter human hepatocytes and hepatoma cell lines. In this study, we developed an HCV-LP-based model system for a systematic functional analysis of antiviral antibodies from patients with acute or chronic hepatitis C. We demonstrate that cellular HCV-LP binding was specifically inhibited by antiviral antibodies from patients with acute or chronic hepatitis C in a dose-dependent manner. Using a library of homologous overlapping envelope peptides covering the entire HCV envelope, we identified an epitope in the N-terminal E2 region (SQKIQLVNTNGSWHI; amino acid positions 408 to 422) as one target of human antiviral antibodies inhibiting cellular particle binding. Using a large panel of serum samples from patients with acute and chronic hepatitis C, we demonstrated that the presence of antibodies with inhibition of binding activity was not associated with viral clearance. In conclusion, antibody-mediated inhibition of cellular HCV-LP binding represents a convenient system for the functional characterization of human anti-HCV antibodies, allowing the mapping of envelope neutralization epitopes targeted by naturally occurring antiviral antibodies. PMID:15308699

  17. Ultrastructural changes in hepatic sinusoidal endothelial cells acutely exposed to colloidal iron.

    Science.gov (United States)

    Bassett, Mark L; Dahlstrom, Jane E; Taylor, Matthew C; Koina, Mark E; Maxwell, Lesley; Francis, Douglas; Jain, Sanjiv; McLean, Allan J

    2003-07-01

    Hepatic sinusoidal endothelial cells form an important interface between the vascular system, represented by the sinusoids, and the space of Disse that surrounds the hepatocyte microvilli. This study aimed to assess the light microscopic and ultrastructural effects of acute exposure of hepatic sinusoidal endothelial cells to colloidal iron by injection of rats with iron polymaltose. Eight minutes after a single intravenous injection of iron polymaltose sinusoidal endothelial cells showed defenestration, and thickening and layering as assessed by transmission electron microscopy. Kupffer cells and stellate cells appeared activated. These changes were not observed in control animals, experiments using equivalent doses of maltose, or experiments using colloidal carbon except for Kupffer cell activation due to colloidal carbon. No significant light microscopic changes were seen in study or control animals. The findings indicate that acute exposure to colloidal iron causes changes in hepatic sinusoidal endothelial cells, stellate cells and Kupffer cells. This may be the result of a direct toxic effect of iron or increased production of reactive oxygen species. These observations suggest a possible mechanism for defenestration of sinusoidal endothelial cells in ageing and in disease states.

  18. Confluent peripheral multiple mononeuropathy associated to acute hepatitis B: a case report

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    CANIELLO Marcello

    2002-01-01

    Full Text Available A thirty three year-old, male patient was admitted at the Hospital of the São Paulo University School of Medicine, at the city of São Paulo, Brazil, with complaint of pains, tingling and decreased sensibility in the right hand for the last four months. This had progressed to the left hand, left foot and right foot, in addition to a difficulty of flexing and stretching in the left foot. Tests were positive for HBeAg, IgM anti-HBc and HBsAg, thus characterizing the condition of acute hepatitis B. The ALT serum level was 15 times above the upper normal limit. Blood glucose, cerebral spinal fluid, antinuclear antibodies (ANA and anti-HIV and anti-HCV serum tests were either normal or negative. Electroneuromyography disclosed severe peripheral neuropathy with an axon prevalence and signs of denervation; nerve biopsy disclosed intense vasculitis. The diagnosis of multiple confluent mononeuropathy associated to acute hepatitis B was done. This association is not often reported in international literature and its probable cause is the direct action of the hepatitis B virus on the nerves or a vasculitis of the vasa nervorum brought about by deposits of immune complexes.

  19. Serum Hyperamylasemia as a prognostic indicator of acute viral hepatitis and cirrhosis of liver

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    N. Kaur

    2014-06-01

    Full Text Available Liver disease is a condition that causes liver inflammation or tissue damage and affects liver function. Liver functions tests are abnormal in various liver diseases such as hepatitis, cirrhosis and end stage liver disease. The study of pancreatic enzymes for prognostic purpose in evolving liver disease is gaining ground and act as prognostic indicator for liver diseases. Present study has been planned to assess the serum amylase status in 50 patients of acute viral hepatitis and 50 patients of cirrhosis of liver in comparison to 50 normal healthy control subjects. Levels of serum amylase were determined by CNP- G3 kinetic method. The serum levels of amylase were significantly raised (p<0.0001 in patients compared to control group and levels were observed to be constantly increased with increased severity of liver diseases. The probable cause of variation in serum amylase enzymes in acute viral hepatitis and cirrhosis of liver is its anatomical proximity and common egress system through Ampulla of vater into the duodenum.

  20. What factors determine the severity of hepatitis A-related acute liver failure?

    Science.gov (United States)

    Ajmera, V.; Xia, G.; Vaughan, G.; Forbi, J. C.; Ganova-Raeva, L. M.; Khudyakov, Y.; Opio, C. K.; Taylor, R.; Restrepo, R.; Munoz, S.; Fontana, R. J.; Lee, W. M.

    2016-01-01

    SUMMARY The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were subgenotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare subgenotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes. PMID:21143345

  1. Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice

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    Jiying Jiang

    2013-08-01

    Full Text Available The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS against acute hepatic ischemia-reperfusion (I/R injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST, malondialdehyde (MDA, and superoxide dismutase (SOD was evaluated by enzyme-linked immunosorbent assay (ELISA. The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury.

  2. Infección aguda por el VHC Acute hepatitis C virus infection

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    A. Martínez Echeverría

    2004-01-01

    Full Text Available La infección aguda por el virus C de la hepatitis produce un cuadro clínico y bioquímico no específico e indistinguible de los causados por otros virus hepatotropos. El diagnóstico específico de la hepatitis aguda por virus C se basa en la detección en sangre del RNA-VHC mediante una técnica de reacción en cadena de la polimerasa cuyo resultado será positivo a partir de 1-2 semanas tras el contacto inicial con el virus. Los anticuerpos frente al VHC se detectan más tardíamente (a las 7-8 semanas por término medio no siendo útiles, como determinación aislada, para distinguir infección aguda de infección crónica o aclaramiento del virus (espontáneo o tras tratamiento. El 55-85% de los pacientes con infección aguda por el VHC no aclaran el virus y desarrollan una infección crónica con riesgo de evolución a cirrosis y de desarrollo de hepatocarcinoma. Por ello, la tendencia actual es tratar con interferón a todos aquellos pacientes en los que el RNA-VHC se mantenga positivo más allá de 3-4 meses tras el diagnóstico de la infección aguda.Acute hepatitis C virus infection produces clinical and biochemical features that is non-specific and indistinguishable from those caused by other hepatotropic viruses. The specific diagnosis of acute hepatitis C virus infection is based on the detection of serum RNA-HCV through a technique of PCR whose result will be positive after 1-2 weeks of the initial contact with the virus. The anti-bodies against HCV are detected later (after 7-8 weeks on average, and are not useful, as an isolated determination, in distinguishing acute infection from chronic infection or in clearing the virus (spontaneous or following treatment. Fifty-five to eighty-five percent of patients with acute HCV infection do not clear the virus and develop a chronic infection with risk of evolution to cirrhosis and of developing hepatocellular carcinoma. For this reason, the present tendency is to treat with interferon

  3. Effect of gomisin A in the prevention of acute hepatic failure induction.

    Science.gov (United States)

    Mizoguchi, Y; Kawada, N; Ichikawa, Y; Tsutsui, H

    1991-08-01

    Nearly all rats develop massive hepatic cell necrosis and die upon intravenous administration of heat-killed Propionibacterium acnes followed by a small amount of Gram-negative lipopolysaccharide 7 days later. However, when such an experimental liver disorder is induced in rats raised for 4 or more weeks on food containing 0.06% of gomisin A extracted and purified from Schizandra chinensis, the survival rate rises, histological changes of the liver improve remarkably, and splenocyte reactivity to phytohemagglutinin and pokeweed mitogen as well as splenocyte interleukin 1 productivity are retained. These results suggested the possibility that the development of acute hepatic failure may be prevented with the oral administration of gomisin A.

  4. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure.

    Science.gov (United States)

    Mhanni, A A; Chan, A; Collison, M; Seifert, B; Lehotay, D C; Sokoro, Ah; Huynh, H Q; Greenberg, C R

    2008-03-01

    We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving.

  5. Remarks on Sasidharan et al. “Evaluation of the Hepatoprotective Effects of Lantadene A, a Pentacyclic Triterpenoid of Lantana Plants against Acetaminophen-induced Liver Damage”. Molecules 2012, 17, 13937-13947

    Directory of Open Access Journals (Sweden)

    Manu Sharma

    2013-03-01

    Full Text Available An article by Sasidharan et al. recently published in the journal Molecules [1] claimed to show the hepatoprotective effects of lantadene A against acetaminophen-induced liver damage in mice. While reading this paper, I came across certain points that need to be clarified and taken up in the interest of science and other scientists working in this area.

  6. Acute hepatitis C infection in HIV-negative men who have sex with men.

    Science.gov (United States)

    McFaul, K; Maghlaoui, A; Nzuruba, M; Farnworth, S; Foxton, M; Anderson, M; Nelson, M; Devitt, E

    2015-06-01

    Acute hepatitis C infection is recognized in HIV-infected men who have sex with men (MSM), but the risk in HIV-negative MSM remains unclear. We evaluated a population of MSM with acute hepatitis C. From January 2010 to May 2014, all cases of HCV antibody positive HIV-negative MSM were identified. European AIDS Network criteria were applied to determine acute infection, and 44 individuals fulfilled the criteria for acute hepatitis C. Ten were RNA negative at baseline and classed as prior spontaneous clearance. 15 (34.1%) had a previously negative HCV antibody within 1 year. 11 (25.0%) had significant elevation in ALT levels, and 18 (40.9%) were clinically diagnosed from risk exposure and history. Median age was 37 years (range 24-75). 41 (93.2%) individuals reported unprotected anal sex, 36 with (87.8%) both insertive and receptive intercourse, 4 (9.8%) with receptive intercourse, 1 (2.4%) with insertive intercourse, and no data were recorded for 3 (7.3%) patients. Individuals had an average of 7.3 reported (median 2, range 1-100) partners. 12 (27.3%) engaged in group sex, 11 (25.0%) practised fisting, 11 (25.0%) admitted using drugs during sexual activity, 16 (36.4%) reported nasal, and 9 (20.5%) reported injection drug use. 14 (31.8)% had unprotected sex whilst under the influence of recreational drugs. 29 individuals were aware of a partner's status. 2 (4.5%) individuals had sexual contact with a known HCV monoinfected partner, 13 (29.5%) with a HIV monoinfected partner and 6 (13.6%) with a HCV/HIV coinfected partner. 9 (20.5%) reported a partner/partners with no known infection. No data were available in 14 (31.8%) individuals. 13 (29.5%) individuals had a coexisting STI at the time of acute HCV diagnosis. 8 (18.2%) received HIV postexposure prophylaxis (PEP) within the 6 months prior to the HCV diagnosis (2 were participants in a HIV pre-exposure prophylaxis trial). 15 (34.1%) individuals achieved spontaneous clearance of HCV, and 11 patients received HCV

  7. 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.

  8. Acute hepatitis in a woman following excessive ingestion of an energy drink: a case report

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    Waked Alain

    2011-06-01

    Full Text Available Abstract Introduction The consumption of energy drinks has increased significantly. We report the case of a patient who presented to our hospital with jaundice, abdominal pain, and markedly increased liver transaminases likely due to the increased consumption of an energy drink. To the best of our knowledge, this is the first case report in the literature linking the development of acute hepatitis to the consumption of an energy drink. Case presentation A 22-year-old Caucasian woman presented to our hospital with epigastric pain, nausea, vomiting, and low-grade fever. She had been drinking 10 cans of an energy drink daily for two weeks prior to presentation. Her physical examination revealed mild epigastric tenderness. Her initial blood tests revealed elevated alanine aminotransferase, aspartate aminotransferase, and total bilirubin. A computed tomographic scan of the abdomen and pelvis was normal, and the patient was discharged to home. She returned to the Emergency Department of our hospital with worsening pain and new-onset jaundice. This time her physical examination revealed epigastric tenderness and icteric sclera. Her aspartate aminotransferase, alanine aminotransferase, and international normalized ratio were markedly elevated. Further radiological studies were non-specific, and she was admitted to our hospital with a diagnosis of acute hepatitis. Her viral serology and toxicology screens were negative. The patient was treated supportively and was discharged after resolution of her symptoms and a marked decrease in her liver enzymes. Conclusion The development of acute hepatitis in this patient was most likely due to the excessive ingestion of an energy drink, and we speculate that niacin was the culprit ingredient.

  9. Protective effect of Curcuma longa L. extract on CCl4-induced acute hepatic stress.

    Science.gov (United States)

    Lee, Geum-Hwa; Lee, Hwa-Young; Choi, Min-Kyung; Chung, Han-Wool; Kim, Seung-Wook; Chae, Han-Jung

    2017-02-01

    The Curcuma longa L. (CLL) rhizome has long been used to treat patients with hepatic dysfunction. CLL is a member of the ginger family of spices that are widely used in China, India, and Japan, and is a common spice, coloring, flavoring, and traditional medicine. This study was performed to evaluate the hepatoprotective activity of CLL extract and its active component curcumin in an acute carbon tetrachloride (CCl4)-induced liver stress model. Acute hepatic stress was induced by a single intraperitoneal injection of CCl4 (0.1 ml/kg body weight) in rats. CLL extract was administered once a day for 3 days at three dose levels (100, 200, and 300 mg/kg/day) and curcumin was administered once a day at the 200 mg/kg/day. We performed alanine transaminase (ALT) and aspartate transaminase (AST). activity analysis and also measured total lipid, triglyceride, and cholesterol levels, and lipid peroxidation. At 100 g CLL, the curcuminoid components curcumin (901.63 ± 5.37 mg/100 g), bis-demethoxycurcumin (108.28 ± 2.89 mg/100 g), and demethoxycurcumin (234.85 ± 1.85 mg/100 g) were quantified through high liquid chromatography analysis. In CCl4-treated rats, serum AST and ALT levels increased 2.1- and 1.2-fold compared with the control. AST but not ALT elevation induced by CCl4 was significantly alleviated in CLL- and curcumin-treated rats. Peroxidation of membrane lipids in the liver was significantly prevented by CLL (100, 200, and 300 mg/kg/day) on tissue lipid peroxidation assay and immunostaining with anti-4HNE antibody. We found that CLL extract and curcumin exhibited significant protection against liver injury by improving hepatic superoxide dismutase (p < 0.05) and glutathione peroxidase activity, and glutathione content in the CCl4-treated group (p < 0.05), leading to a reduced lipid peroxidase level. Our data suggested that CLL extract and curcumin protect the liver from acute CCl4-induced injury in a rodent model by suppressing hepatic

  10. Parovirus B19 infection in an HIV-infected patient with febrile pancytopenia and acute hepatitis.

    Science.gov (United States)

    Alliot, C; Barrios, M; Taib, J; Brunel, M

    2001-01-01

    The case of a 34-year-old male patient with HIV infection referred for severe febrile pancytopenia is reported. Clinical and laboratory evaluations revealed acute hepatitis B infection and concomitant parvovirus B19 infection. The patient died just before treatment with immune globulin was to be administered. Parvovirus B19 has been found to cause a wide variety of hematologic disorders such as neutropenia, thrombocytopenia, pancytopenia, and hemophagocytic syndrome. The role of parvovirus B19 in the pathogenesis of bone marrow or liver involvement is briefly discussed.

  11. Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?

    Institute of Scientific and Technical Information of China (English)

    Kilian Weigand; Carina Riediger; Wolfgang Stremmel; Christa Flechtenmacher; Jens Encke

    2007-01-01

    While cardiopulmonary symptoms are common in patients undergoing classical or, due to physical exercise,exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio (INR). No other causes for liver failure could be identified but physical exhaustion and hyperthermia.

  12. Efficacy of immunization against hepatitis B virus infection in acute leukemia

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    Tuphan Kanti Dolai

    2010-09-01

    Full Text Available Objective: The aim of this study was to assess the antibody response to combined passive-active immunization versus active immunization against hepatitis B in 71 patients with acute leukemia with negative hepatitis B virus serology at presentation. Materials and Methods: The first group (n=28 received a double dose of hepatitis B vaccine at 0, 1, 2 and 6 months and immunoglobin (HBIG at 0 and 1 month concurrently with vaccine but at a different intramuscular site. The second group (n=43 received double dose of hepatitis B vaccine at 0, 1, 2, and 6 months. HBsAg and anti-HBs titers were determined one month after the 1st, 2nd, 3rd and 4th doses of vaccine. Results: In the vaccine-only group, 2.56%, 8.33%, 14.28% and 34.29% of patients developed anti-HBs titer ≥10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. In the HBIG group, 91.30%, 91.30%, 69.56% and 73.91% of patients developed anti-HBs titer ≥10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. Those in the vaccine-HBIG group maintained their anti-HBs titer ≥10 IU/L from the 1st to the 4th doses. In the vaccine-only group, 34.29% of patients gained protective antibody titer after receiving the 4th dose of vaccine. Subgroup analysis of age (pediatric vs adult and disease (acute lymphoblastic leukemia vs acute myeloid leukemia groups showed no effect of either on the development of protective antibody titer. The incidence of HBsAg positivity one month after the 4th dose of vaccine was 8.62%. No patient became positive for anti-HCV or HIV antibody before or after chemo therapy.Conclusion: Combined HBIG and vaccine may protect acute leukemia patients during the intensive chemotherapy period.

  13. Acute Viral Hepatitis E Is Associated with the Development of Myocarditis

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    M. Premkumar

    2015-01-01

    Full Text Available Myocarditis, an inflammatory disease of heart muscle, is an important cause of dilated cardiomyopathy worldwide. Viral infection is an important cause of myocarditis. This condition presents with various symptoms, ranging from minimally symptomatic cases to fatal arrhythmia and cardiogenic shock, and may develop chronic myocarditis and dilated cardiomyopathy in some patients. We report the case of a 26-year-old patient with acute viral hepatitis E who developed symptomatic myocarditis. As far as we could search, this is probably the 3rd case report of this rare association.

  14. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930140 Hepatocyte stimulator peptide and itsclinical significance in viral hepatitis.ZHOUWeiping(周卫平),et al.Instit Viral Hepatitis,Chongqing Med Univ,630010.Chin J InternMed 1992;31(10):626-628.Hepatocyte stimulator peptide(HSP)is anewly developed hepatic stimulator substance.Its monoclonal antibodies have been obtained inour laboratory.In this study,HSP was deter-mined in the sera of 315 subjects including pa-

  15. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010349 Relationships between serum hepatitis B virus load in mothers,free maternal DNA in peripheral blood of newborns and hepatitis B virus infection of newborns. WEI Junni(魏俊妮),et al. Dept Epidemiol,Shanxi Med Univ,Taiyuan 030001. Chin J Infect Dis 2010;28(5):297-300. Objective To study the relationships between serum hepatitis B virus (HBV) DNA level

  16. Acute lung injury following transcatheter hepatic arterial chemoembolization of doxorubicin-loaded LC beads in a patient with hepatocellular carcinoma

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    Ihsan Khan

    2012-01-01

    Full Text Available Transcatheter arterial chemoembolization (TACE currently is being used as an effective palliative therapy for unresectable cancers especially hepatocelluar carcinoma (HCC. Accidental lipiodol embolism to the lungs is a rare but potentially fatal complication of TACE. This procedure involves injection of drug-eluting microspheres (LC Bead loaded with doxorubicin, followed by embolization with embozene microspheres until stasis is evident, being used in advanced HCC. We report a patient with inoperable HCC with underlying Hepatitis C and liver cirrhosis, who developed acute lung injury following targeted chemoembolization of selective feeding hepatic artery with LC beads loaded with doxorubicin. Acute lung injury as a complication of unintended lung chemoembolization with doxorubicin has not been previously reported in the literature. Interventional radiologists screen patients for potential hepatic A-V shunt and take appropriate precautions to prevent unintended pulmonary embolization. These include appropriate selection of LC bead particle size especially in patients who are embolized with radiation pellets. This report highlights the need for a screening total body scintigraphy after injection of radionuclide Tc-99 MAA in the feeding hepatic artery to identify patients with hepatic A-V shunt. In such patients, appropriate size selection of LC bead particles is critical to prevent unintended pulmonary chemoembolization and acute lung injury. Other measures include careful patient selection, low dose of chemotherapy, and transient selective hepatic vein balloon occlusion.

  17. Acute onset anarthria without hepatic manifestation: a rare presentation of Wilson disease.

    Science.gov (United States)

    Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S

    2013-08-20

    Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. Acute onset anarthria as the heralding and predominant presenting feature has been rarely reported in the literature. We reported a case of a 12-year-old girl who presented with acute onset anarthria and dystonia of 1-month duration. On further evaluation, a diagnosis of WD was made. The patient showed partial improvement after she was started on copper chelating agents and anticholinergics.

  18. An outbreak of acute hepatic encephalopathy due to severe aflatoxicosis in Malaysia.

    Science.gov (United States)

    Lye, M S; Ghazali, A A; Mohan, J; Alwin, N; Nair, R C

    1995-07-01

    In October 1988, 13 Chinese children died of acute hepatic encephalopathy in the northwestern state of Perak in peninsular Malaysia. The acuteness of the illness differed from previously reported outbreaks described in Kenya, India, and Thailand. Epidemiologic investigations determined that the children had eaten a Chinese noodle, loh see fun, hours before they died. The attack rates among those who had eaten the noodles were significantly higher than those who had not (P < 0.0001). The cases were geographically scattered in six towns in two districts along the route of distribution of the noodle supplied by one factory in Kampar town. Aflatoxins were confirmed in postmortem samples from patients. This outbreak has important public health implications for many developing countries.

  19. Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

    Institute of Scientific and Technical Information of China (English)

    Fan ZHANG; Yongwen HE; Zhongping DUAN

    2008-01-01

    The role of the high mobility group box 1 (HMGB-1) in acute hepatic failure and the ef- fect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were detected by the enzyme linked immunosorbent assay (ELISA), the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system (P<0.05). It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.

  20. Alterations in bronchoalveolar lavage fluid during ischemia-induced acute hepatic failure in the pig.

    Science.gov (United States)

    Kostopanagiotou, Georgia; Routsi, Christina; Smyrniotis, Vassilios; Lekka, Marilena E; Kitsiouli, Eirini; Arkadopoulos, Nikolaos; Nakos, George

    2003-05-01

    The objective of this controlled experimental animal study was to evaluate whether acute hepatic failure (AHF) can cause acute lung injury (ALI) and to investigate possible pathophysiologic mechanisms. Seventeen domestic pigs were randomly assigned to AHF and sham groups. AHF was induced by surgical devascularization of liver in 10 animals. Seven animals were sham operated. Hemodynamics, lung mechanics, extravascular lung water (EVLW), and intracranial pressure, blood gas, liver function tests, and serum endotoxin levels were measured. Cells count, total protein, and phospholipids and phospholipases A(2) were determined in the bronchoalveolar lavage (BAL) fluid. Measurements were obtained after the insertion of central lines and 4 hours and 7 hours after the completion of the surgical procedure. Hemodynamic, biochemical, neuromonitoring, and histologic data confirmed the development of liver failure. Seven hours after devascularization, EVLW was higher in AHF (13.7 +/- 1.8 mL/kg) compared with the sham group (5.9 +/- 0.7 mL/kg) (P <.05); in AHF, increase of neutrophils (5% +/- 8% to 25% +/- 8%, P <.001), total protein (6.2 +/- 3.7 to 11.2 +/- 6.5 microg/mL, P <.048), and phospholipase A(2) (1.43 +/- 0.56 to 2.38 +/- 1.38 nmoL/mL/h, P <.03) and decrease in PAF-acetylhydrolase (0.114 +/- 0.128 to 0.039 +/- 0.038 nmol/mL/h, P <.01) compared with baseline were observed; total phospholipids decreased in AHF and increased in the sham model. Histologic examination confirmed lesions compatible with acute lung injury. In conclusion, AHF due to hepatic devascularization induced acute lung injury, confirmed by the increase of inflammatory cells in the alveoli as well as by histologic findings. The decreased PAF-AcH and the increased phospholipase A(2) may play a significant role in the perpetuation of inflammation accompanied by surfactant disorders.

  1. Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load

    OpenAIRE

    Kenji Ando; Soo Ryang Kim; Susumu Imoto; Taisuke Nakajima; Keiji Mita; Katsumi Fukuda; Miyuki Taniguchi; Noriko Sasase; Akira Muramatsu; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2009-01-01

    Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 μg) plus a daily oral dose of RBV (60...

  2. Does Fasciola hepatica infection modify the response of acute hepatitis C virus infection to IFN-α treatment?

    Science.gov (United States)

    Sahin, Mehmet; Isler, Mehmet; Senol, Altug; Demirci, Mustafa; Aydın, Zeynep Dilek

    2005-01-01

    Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response. Fasciola infection could theoretically interfere with the Th1 immune response, even when acquired after an initial response to interferon-alpha treatment for acute hepatitis C virus (HCV) infection. We report here the case of a male patient who acquired Fasciola hepatica infection after an initial response to IFN-alpha therapy with a favorable outcome PMID:16437701

  3. Does Fasciola hepatica infection modify the response of acute hepatitis C virus infection to IFN-α treatment?

    Institute of Scientific and Technical Information of China (English)

    Mehmet Sahin; Mehmet Isler; Altug Senol; Mustafa Demirci; Zeynep Dilek Aydin

    2005-01-01

    Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response. Fasciola infection could theoretically interfere with the Th1 immune response, even when acquired after an initial response to interferon-alpha treatment for acute hepatitis C virus (HCV) infection. We report here the case of a male patient who acquired Fasciola hepatica infection after an initial response to IFN-alpha therapy with a favorable outcome

  4. The Protective Effect of Resveratrol on Concanavalin-A-Induced Acute Hepatic Injury in Mice

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    Yingqun Zhou

    2015-01-01

    Full Text Available Pharmacologic Relevance. Resveratrol, an antioxidant derived from grapes, has been reported to modulate the inflammatory process. In this study, we investigated the effects of resveratrol and its mechanism of protection on concanavalin-A- (ConA- induced liver injury in mice. Materials and Methods. Acute autoimmune hepatitis was induced by ConA (20 mg/kg in Balb/C mice; mice were treated with resveratrol (10, 20, and 30 mg/kg daily by oral gavage for fourteen days prior to a single intravenous injection of ConA. Eight hours after injection, histologic grading, proinflammatory cytokine levels, and hedgehog pathway activity were determined. Results. After ConA injection, the cytokines IL-2, IL-6, and TNF-α were increased, and Sonic hedgehog (Shh, Glioblastoma- (Gli- 1, and Patched (Ptc levels significantly increased. Pretreatment with resveratrol ameliorated the pathologic effects of ConA-induced autoimmune hepatitis and significantly inhibited IL-2, IL-6, TNF-α, Shh, Gli-1, and Ptc. The effects of resveratrol on the hedgehog pathway were studied by western blotting and immunohistochemistry. Resveratrol decreased Shh expression, possibly by inhibiting Shh expression in order to reduce Gli-1 and Ptc expression. Conclusion. Resveratrol protects against ConA-induced autoimmune hepatitis by decreasing cytokines expression in mice. The decreases seen in Gli-1 and Ptc may correlate with the amelioration of hedgehog pathway activity.

  5. Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis.

    Science.gov (United States)

    Omar, Hany A; Mohamed, Wafaa R; Arab, Hany H; Arafa, El-Shaimaa A

    2016-01-01

    Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.

  6. Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis.

    Directory of Open Access Journals (Sweden)

    Hany A Omar

    Full Text Available Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST, inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α and enhancement of interleukin-10 (IL-10. Meanwhile, it lowered malondialdehyde (MDA, nitric oxide (NO and nuclear factor erythroid 2-related factor 2 (NRF-2 levels with restoration of glutathione (GSH, and glutathione peroxidase (GPx. Regarding mitogen-activated protein kinase (MAPK pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK and phospho-extracellular signal-regulated kinase (p-ERK1/2 in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.

  7. Hepatitis

    Science.gov (United States)

    ... inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There are at least 5 hepatitis viruses. Hepatitis A is contracted when a child eats food or drinks water that is contaminated with the virus or has ...

  8. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970349 Primary structure and variability of partialsequences in nonstructural gene 5 region of hepatitis Gvirus, CHANG Jinhong(常锦红), et al. Hepatol Instis,People’s Hosp, Beijing Med Univ, Beijing, 100044. NatlMed J China 1997; 77(3): 178-182. Objective: To sequence partial genome of hepatitis G

  9. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009209 Effects of chronic hepatitis B virus infection on human hepatic cytochrome P450 2C9.ZHO Fuping(周福平),et al.Dept Infect Dis,Shanghai Changzheng Hosp,Shanghai 200003.Chin J Infect Dis,2009;27(2):94-98.

  10. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920691 The determination of serum hepa-titis B virus DNA by polymerase chain rea-ction in hepatitis B patients treated withalpha-interferon. XU. Jianye(徐建业), et al.Centr Lab, Chongqing Cancer Instit, 630030.Chin J Intern Med, 1992; 31(5): 278-280. To clarify the status of HBV in serum of

  11. 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

  12. Clinical significance of elevated serum alpha-fetoprotein (AFP) level in acute viral hepatitis A (AHA).

    Science.gov (United States)

    Seo, Seung In; Kim, Su Sun; Choi, Bo Youn; Lee, Sang Ho; Kim, Sung Jun; Park, Hye Won; Kim, Hyoung Su; Shin, Woon Geon; Kim, Kyung Ho; Lee, Jin Heon; Kim, Hak Yang; Jang, Myoung Kuk

    2013-10-01

    The clinical course of acute viral hepatitis A (AHA) is highly variable. Serum alphafetoprotein (AFP) level is often elevated in various types of acute liver injuries, indicating active liver regeneration. This study was aimed to investigate the clinical significance of serum AFP level in the aspect of the early recovery in AHA. A total of 238 patients with AHA, confirmed by IgM anti-hepatitis A virus, were included. The patients were classified according to serum AFP level. Multivariate analysis by Cox proportional hazards model using dichotomized clinical variables was performed to identify the independent predictors for early recovery (ALT normalization within 2 weeks). The median age (range) was 30 (17-50) years and male dominant (62%, 147/238). Compared to low AFP group, high AFP group (>10 ng/mL) had significantly lower platelet counts (p 10 ng/mL) was the only independent predictor for early recovery (Hazard ratio (HR); 2.392, 95% CI; 1.564-3.659, p = 0.0001). High serum AFP level (>10 ng/mL) may indicate the already-started recovery through active liver regeneration or the early recovery within 2 weeks in AHA.

  13. Atg7 Knockdown Augments Concanavalin A-Induced Acute Hepatitis through an ROS-Mediated p38/MAPK Pathway.

    Directory of Open Access Journals (Sweden)

    Yan Zhuang

    Full Text Available Concanavalin A (ConA, a T-cell mitogen that induces acute autoimmune hepatitis, is widely used to model pathophysiological processes of human acute autoimmune liver disease. Although autophagy has been extensively studied in the past decade, little is known about its molecular mechanism underlying the regulation of ConA-induced acute hepatitis. In this study, we used a Cre-conditional atg7 KO mouse to investigate the effects of Atg7-associated autophagy on ConA-induced murine hepatitis. Our results demonstrated that atg7 deficiency in mice enhanced macrophage activation and increased pro-inflammatory cytokines upon ConA stimulation. Atg7 silencing resulted in accumulation of dysfunctional mitochondria, disruption of reactive oxygen species (ROS degradation, and increase in pro-inflammatory cytokines in Raw264.7 cells. p38/MAPK and NF-κB levels were increased upon ConA induction due to Atg7 deficiency. Blocking ROS production inhibited ConA-induced p38/IκB phosphorylation and subsequent intracellular inflammatory responses. Hence, this study demonstrated that atg7 knockout in mice or Atg7 knockdown in cell culture augmented ConA-induced acute hepatitis and related cellular malfunction, indicating protective effects of Atg7 on regulating mitochondrial ROS via a p38/MAPK-mediated pathway. Collectively, our findings reveal that autophagy may attenuate macrophage-mediated inflammatory response to ConA and may be the potential therapeutic targets for acute liver injury.

  14. Mechanism research on the effects of fasudil to postoperative acute hepatic failure induced by hepatic ischemia & hepatectomy on rats with obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    Shao-Hua Chen; Li Cheng

    2015-01-01

    Objective:To establish a kind of animal model of postoperative acute hepatic failure induced by hepatic ischemia & hepatectomy on rats with obstructive jaundice, which could show similar clinical pathophysiological changes in hunman beings. To investigate the influence of fasudil to this model.Method:Selected 96 Wistar big rats as animal model of obstructive jaundice, which were treated with ligation and cuting off common bile duct. Rats in low-dose group were immediately injected fasudil of 10 mg/kg through portal vein after hepatectomy, while rats in high-dose group were immediately injected fasudil of 30 mg/kg through portal vein after hepatectomy, rats in control group were immediately injected equivalent normal saline through portal vein after hepatectomy. To determine the serum ALT, AST, TBIL (tumor necrosis factor-α, TNF-α)and (interferon-γ, INF-γ) levels in postoperative rats with hepatic failure within 6 h; to determine the (superoxide dismutase, SOD) activity and (malondialdehyde, MDA) content in hepatic tissue; hepatic tissue HE staining to observe the pathological injury; to observe animal model 96 h of survival rate.Results:That Proceeding internal biliary drainage operation to rats after obstruction for 14 h, and blocking 70% of hepatic blood supply, excising remnant liver after 30 min was in accordance with criteria of hepatic failure animal, and was deserved to further research. Compared with control group, serum AST, ALT, TBIL, TNF-α, INF-γ levels decreased in fasudil treatment group, SOD activity increased in hepatic tissue, MDA content decreased, pathological injury in hepatic tissue reduced, rats 96 h of survival rate increased, and the effects of high-dose group were more obvious than that in low-dose group.Conclusion:A surgical hepatic failure model in rat was established, which showed similar clinical pathophysiological changes in hunman beings. In addition, we have found that fasudil possibly played a role of protection to hepatic

  15. Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis The Dangers of Hepatitis: What you should know from A to E ... drugs. In some cases, hepatitis lasts a lifetime. Hepatitis: Acute or Chronic? Acute hepatitis is the initial ...

  16. Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver

    Directory of Open Access Journals (Sweden)

    Patricia Rivera

    2017-10-01

    Full Text Available Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE-peroxisome proliferators activated receptor alpha (PPARα system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP, a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system. A dose-response (0.5–5–10–20 mM and time-course (2–6–24 h study in human HepG2 cells showed a biphasic response, with a decreased PPARα expression after 6-h APAP incubation followed by a generalized increase of NAE-PPARα system-related components (PPARα, NAPE-PLD, and FAAH, including the NAEs oleoyl ethanolamide (OEA and docosahexaenoyl ethanolamide, after a 24-h exposure to APAP. These results were partially confirmed in a time-course study of mice exposed to an acute dose of APAP (750 mg/kg. The gene expression levels of Pparα and Faah were decreased after 6 h of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah, as well as the liver levels of OEA and palmitoyl ethanolamide, were increased. Repeated APAP administration (750 mg/kg/day up to 4 days also decreased the expression levels of PPARα and FAAH, and increased the liver levels of NAEs. A resting period of 15 days completely restored these impairments. Liver immunohistochemistry in a well-characterized human case of APAP hepatotoxicity confirmed PPARα and FAAH decrements. Histopathological and hepatic damage (Cyp2e1, Caspase3, αSma, Tnfα, and Mcp1-related alterations observed after repeated APAP administration were aggravated in the liver of Pparα-deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARα signaling system is implicated in liver

  17. Multiplex polymerase chain reaction test for the diagnosis of acute viral hepatitis A.

    Science.gov (United States)

    Heo, Nae-Yun; Lim, Young-Suk; An, Jihyun; Ko, Sun-Young; Oh, Heung-Bum

    2012-12-01

    The early diagnosis of acute hepatitis A (AHA) is hindered because serum IgM against hepatitis A virus (HAV) can yield false-negative results during the window period. This study evaluated the diagnostic accuracy of a polymerase chain reaction (PCR) kit for HAV RNA for the diagnosis of AHA. Samples were collected from 136 patients with acute severe hepatitis at their admission to Asan Medical Center between June 2010 and July 2010. Samples were analyzed for serum IgM anti-HAV using an immunoassay test and for qualitative HAV RNA using the Magicplex HepaTrio PCR test kit. The diagnostic accuracies of these methods were tested on the basis of clinical and laboratory diagnoses of AHA. The concordance rate and kappa value between IgM anti-HAV and HAV RNA PCR were 88.2% and 0.707, respectively. For the diagnosis of AHA, the sensitivity and specificity of IgM anti-HAV were 90.7% and 100%, respectively, when an "equivocal" result was regarded as positive; and 79.1% and 100%, respectively, when an "equivocal" result was regarded as negative. The sensitivity and specificity of HAV RNA PCR were 81.4% and 100%, respectively. All four patients with negative IgM anti-HAV and positive HAV RNA PCR results and all four patients with equivocal IgM anti-HAV RNA and positive HAV RNA PCR results were eventually diagnosed with AHA. The qualitative HAV RNA PCR test has an equivalent diagnostic accuracy for AHA compared to IgM anti-HAV and may be more sensitive during the window period.

  18. Acute outflow obstruction of hepatic veins in rabbits: quantitative analysis of hepatic perfusion with contrast-enhanced sonography.

    Science.gov (United States)

    Kim, Kyoung Won; Kim, Pyo Nyun; Shin, Ji Hoon; Shin, Dong Ho; Jeong, Woo Kyoung; Won, Hyung Jin; Shin, Yong Moon; Lee, Won Jae; Lee, Moon Gyu; Song, Gi-Won; Hwang, Shin; Lee, Sung-Gyu

    2011-05-01

    To compare time-enhancement curve parameters of contrast-enhanced sonography in acute partial hepatic venous outflow obstruction with those of a baseline study. Contrast-enhanced sonography was performed in 11 rabbits with bolus administration of a sulfur hexafluoride contrast agent (0.1 mL/kg). After baseline scanning for 3 minutes, a 5.3F balloon catheter was placed into the left hepatic vein. Obstruction was artificially induced by 0.4-mL balloon inflation, and sonography was repeatedly performed thereafter. On images stored with 1-second intervals, 2 × 2-mm regions of interest were placed, and mean luminosity was measured. Time-enhancement curves were plotted, and contrast arrival times, peak enhancement values, peak enhancement times, 50% wash-out times, and 3-minute wash-out rates were obtained. Paired t tests were performed to evaluate the significance of differences in the parameters between baseline and obstruction. On baseline sonography, the median contrast arrival time, peak enhancement value, peak enhancement time, 50% wash-out time, and 3-minute wash-out rate were 6 (range, 4-8; mean ± SD, 5.9 ± 1.2) seconds, 188.5 (104.7-209.5; 178.4 ± 33.1) arbitrary units, 19 (14-27; 19.8 ± 4.1) seconds, 75 (60-101; 78.2 ± 13.9) seconds, and 89.7% (81.3%-95.1%; 88.4% ± 4.9%), respectively. With obstruction, those values were 7 (5-12; 6.9 ± 2.3) seconds, 202.8 (98.2-215.1; 186.0 ± 39.3) arbitrary units, 31 (17-59; 32 ± 11.6) seconds, 101 (47-136; 96.2 ± 23.6) seconds, and 79.2% (66.2%-88.8%; 79.1% ± 7.6%). Compared with baseline, the peak enhancement time was significantly delayed from 19 to 31 seconds (P = .0027), 50% wash-out time significantly delayed from 75 to 101 seconds (P = .0209), and 3-minute wash-out rate significantly decreased from 89.7% to 79.2% (P rate is decreased in rabbits with artificially induced obstruction compared with a baseline study.

  19. 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.

  20. Sustained viral response of a case of acute hepatitis C virus infection via needle-stick injury

    Institute of Scientific and Technical Information of China (English)

    Takayuki Kogure; Yu Nakagome; Masashi Ninomiya; Tooru Shimosegawa; Yoshiyuki Ueno; Noriatsu Kanno; Koji Fukushima; Yoko Yamagiwa; Futoshi Nagasaki; Eiji Kakazu; Yasunori Matsuda; Osamu Kido

    2006-01-01

    A 29-year-old nurse with a hepatitis C virus (HCV) infection caused by needle-stick injury was treated with interferon-beta starting about one year after the onset of acute hepatitis. The patient developed acute hepatitis C with symptoms of general fatigues, jaundice, and ascites 4 wk after the needle-stick injury. When these symptoms were presented, the patient was pregnant by artificial insemination. She hoped to continue her pregnancy.After delivery, biochemical liver enzyme returned to normal levels. Nevertheless, HCV RNA was positive and the pathological finding indicated a progression to chronicity. The genotype was 1b with low viral load.Daily intravenous injection of interferon-beta at the dosage of six million units was started and continued for eight weeks. HCV was eradicated without severe adverse effects. In acute hepatitis C, delaying therapy is considered to reduce the efficacy but interferon-beta therapy is one of the useful treatments for hepatitis C infection in chronic phase.

  1. Acute hepatitis C in Spain: a retrospective study of 131 cases Hepatitis aguda C en España: estudio retrospectivo de 131 casos

    OpenAIRE

    Ramón Pérez-Álvarez; Javier García-Samaniego; Ricard Solà; Rosa Pérez-López; Rafael Bárcena; Ramón Planas; Nuria Cañete; María Luisa Manzano; María Luisa Gutiérrez; Luis Morano; Luis Rodrigo

    2012-01-01

    Background and aims: the management of acute hepatitis C (AHC) is controversial. We have conducted a retrospective study to determine the epidemiological and biochemical aspects, the genotypes, the spontaneous clearance of HCV (SVC), and the treatment responses in patients with AHC. Methods: we have retrospectively collected data from 131 patients with AHC from 18 Spanish hospitals. Results: the mean age was 43 ± 16 years (17-83), 69% were symptomatic. The causes of infection were noso...

  2. Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection

    Directory of Open Access Journals (Sweden)

    Megan L. Lawlor

    2016-01-01

    Full Text Available Intrahepatic cholestasis of pregnancy (ICP is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing was performed. Patient delivered vaginally at 33-week gestation following preterm rupture of membranes. Neonates were admitted to NICU and had uncomplicated neonatal courses. In the setting of ICP with significant transaminitis and severe elevation of bile acids, consideration of acute viral hepatitis is important, especially considering the worsening opioid epidemic and concurrent increase in intravenous drug use in the United States. Further study is needed regarding the acute form of HCV infection and its effect on ICP and associated bile acids.

  3. Peginterferon-alfa mono-therapy in the treatment of acute hepatitis C in HIV-infection

    NARCIS (Netherlands)

    Boesecke, C.; van Assen, S.; Stellbrink, H. -J.; Baumgarten, A.; Ingiliz, P.; Strassburg, C. P.; Schwarze-Zander, C.; Wasmuth, J. -C.; Hoepelman, A. I. M.; Rockstroh, J. K.; Arends, J. E.

    2014-01-01

    The ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal treatment outcome in HIV co-infected individuals. Cohort study of 105 HIV-infected patients with AHC infection from five centres in two European countries was carried out.

  4. A 12-Week Treatment with Boceprevir, Peginterferon and Ribavirin for Acute Hepatitis C in HIV infected patients

    NARCIS (Netherlands)

    Hullegie, Sebastiaan J; Claassen, Mark A A; van den Berk, Guido E L; van der Meer, Jan T M; Posthouwer, Dirk; Lauw, Fanny N; Leyten, Eliane M S; Koopmans, Peter P; Richter, Clemens; van Eeden, Arne; Bierman, Wouter F W; Newsum, Astrid M; Arends, Joop E; Rijnders, Bart J A

    2016-01-01

    BACKGROUND AND AIMS: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men (MSM) and generally treated with peginterferon-alfa (pegIFN) and ribavirin (RBV) during 24 weeks. The addition of a protease inhibitor could shorten therapy without loss of efficac

  5. Acute effects of ethanol on hepatic uptake and distribution of narcotics in the isolated perfused rabbit liver

    Energy Technology Data Exchange (ETDEWEB)

    Kreek, M.J.; Rothschild, M.A.; Oratz, M.; Mongelli, J.; Handley, A.C.

    This study was performed as an initial step in systematically defining the hepatic interactions between ethanol and opioids using a controlled in vitro system. The acute effects of ethanol on the initial uptake and distribution of long- and short-acting narcotics were studied using isolated rabbit liver perfused with rabbit blood without or with ethanol. A pulse injection of 1.5 mg of 14C-labeled narcotic (methadone, 1-alpha-acetylmethadol (LAAM), morphine, or meperidine) was made into the portal vein cannula followed by perfusion for 2 min. Radioactivity was determined in liver homogenates and subcellular fractions; methadone and its metabolites were measured by thin-layer chromatography with zonal scanning in each fraction. Ethanol preperfusion and concomitant ethanol perfusion did not effect hepatic uptake of methadone, LAAM, morphine, or meperidine. Although subcellular localization of morphine and meperidine differed from that of methadone and LAAM, perfusion with ethanol did not alter the acute hepatic uptake and distribution of any of the narcotics. These findings suggest that acute exposure to ethanol does not alter the acute hepatic disposition of narcotics.

  6. Treatment of acute hepatitis C virus infection in HIV+ patients: Dutch recommendations for management.

    Science.gov (United States)

    Arends, J E; Lambers, F A E; van der Meer, J T M; Schreij, G; Richter, C; Brinkman, K; Hoepelman, A I M

    2011-01-01

    With a rising incidence of acute hepatitis C virus (HCV) infection in patients coinfected with the human immunodeficiency virus (HIV), there is a need for evidence-based treatment recommendations. There are no randomised trials available and published studies differ with respect to design, patient characteristics and number of patients included, making a comparison between studies difficult. However, it is critical to standardise treatment for this group of patients in order to optimise the outcome of therapy. The Dutch Society for HIV Physicians proposed to write recommendations for the treatment of acute HCV in HIV -coinfected patients. Combination therapy with pegylated interferon-alpha and ribavirin is the preferred regimen initiated preferably within 12 weeks after the diagnosis of acute HCV. A treatment duration of 24 weeks is recommended in case of a favourable virological response (either achievement of a rapid virological response or a > 2 log10 decrease plus undetectable HCV-RNA at week 12). In all other patients prolonging the duration of therapy to 48 weeks should be considered.

  7. HEPATOPROTECTIVE EFFECT OF AQUEOUS AND N-HEXANE EXTRACT OF NIGELLA SATIVA IN PARACETAMOL (ACETAMINOPHEN INDUCED LIVER DISEASES OF RATS: A HISTOPATHOLOGICAL EVALUATION

    Directory of Open Access Journals (Sweden)

    Farida Yesmin

    2013-07-01

    Full Text Available Acute over dose of paracetamol (acetaminophen causes serious hepatic necrosis. So, this study was conducted to observe the hepatoprotective activity of aqueous and n-hexane extract of Nigella sativa in paracetamol induced hepatotoxicity in rats in Dhaka, Bangladesh from 2008 to 2010. Single dose of paracetamol was administered on day one and rats were sacrificed on day three. Liver damage was evaluated by hepatic histology. Aqueous and n-hexane extract of Nigella sativa was administered orally into two other rat groups through intra-gastric tube for 28 days in which paracetamol was administered orally on day 28 and were sacrificed on day 30. Liver of all rats were excised and processed for light microscopy with a view to histopathological evaluation. The histological examination of the liver tissues in vehicle treated group and paracetamol-control group of rats showed normal hepatic architecture, centrilobular necrosis, polymorph (neutrophils infiltration and pyknosis of the hepatocytes respectively. The hepatic architecture of rats pre-treated with aqueous extract of Nigella sativa showed improvement of necrosis with very few pyknotic nuclei when compared to the paracetamol-control group. The hepatic architecture of rats pre-treated with aqueous extract as well as with the n-hexane extract of Nigella sativa did not show pyknotic nuclei and polymorph infiltration while apparently regenerating hepatocytes, visible under the microscope. Aqueous extract and n-hexane extract of Nigella sativa extended hepatoprotection by reducing oxidative stress in experimental liver damage in rats. Furthermore, the protection afforded by the n-hexane extract of Nigella sativa pre-treated group was superior to the aqueous extract of Nigella sativa pre-treated group.

  8. Usefulness of B-mode and doppler sonography for the diagnosis of severe acute viral hepatitis A.

    Science.gov (United States)

    Shin, Sang Wook; Kim, Tae Yeob; Jeong, Woo Kyoung; Kim, Yongsoo; Kim, Jinoo; Kim, Young Hwan; Park, Hwan Cheol; Sohn, Joo Hyun

    2015-01-01

    To investigate B-mode and Doppler ultrasonography (US) features correlating with laboratory findings for the diagnosis of severe acute hepatitis (SAH) in patients with hepatitis A virus infection. Thirty-nine consecutive serologically proven patients were enrolled. Decreased parenchymal echotexture, periportal tracking, gallbladder wall change, and splenomegaly were assessed on B-mode images. Blood flow velocities were measured in the main portal (V(PORTAL)) and in the hepatic veins, and the hepatic venous pulsatility index was calculated. SAH was defined as high model for end-stage liver disease (MELD) score ≥ 15 with or without coagulopathy. The relationship between US features and laboratory findings was assessed, and SAH diagnosis was evaluated. Serum alanine transaminase and prothrombin time were significantly different depending on the presence of gallbladder wall change and splenomegaly (p hepatic venous waveform and hepatic venous pulsatility index were significantly correlated with MELD score. For the diagnosis of SAH, the area under the receiver operating characteristic curve of V(PORTAL) was 0.798. It reached 0.869 in the patients with typical GB change. Both B-mode and Doppler US correlated well with several laboratory variables and may be helpful to diagnose SAH in patients with hepatitis A virus infection. © 2014 Wiley Periodicals, Inc.

  9. Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study.

    Directory of Open Access Journals (Sweden)

    Behzad Hajarizadeh

    Full Text Available Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection.Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study. Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels ≤ 120 days were categorised by a priori-defined patterns of HCV RNA levels: i spontaneous clearance, ii partial viral control with persistence (≥ 1 log IU/mL decline in HCV RNA levels following peak and iii viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak. Factors associated with HCV RNA patterns were assessed using multinomial logistic regression.Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%, partial viral control with persistence (27%, and viral plateau with persistence (41%. HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P = 0.018. In the two groups with persistence, Interferon lambda 3 (IFNL3 CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02. In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83.Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate

  10. 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.

  11. A Complicated Course of Acute Viral Induced Pharyngitis, Icteric Hepatitis, Acalculous Cholecystitis, and Skin Rash

    Directory of Open Access Journals (Sweden)

    Fereshte Sheybani

    2016-01-01

    Full Text Available This case reveals the complexities and challenges in the diagnosis of acute Epstein-Barr virus (EBV infection, indicating the potential relationship between EBV infection and severe icteric hepatitis, acalculous cholecystitis, and lymphocytic vasculitis. We suggest including EBV infectious mononucleosis in the list of differential diagnoses when any of these clinical syndromes (or a combination thereof occurs without apparent cause, especially in the presence of lymphocytosis. To our knowledge, this is the first report to suggest the possible role of EBV in the pathogenesis of cutaneous lymphocytic vasculitis. Also it is possible that EBV infection triggered the flare-up of the underlying rheumatologic disease. Therefore, it could be assumed that a part of the clinical syndrome (e.g., dermatologic manifestations might be related to the flare-up of the underlying rheumatologic disease.

  12. A Case of Acute Q Fever Hepatitis Diagnosed by F-18 FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Beak, Sora [Hallym Univ. College of Medicine, Seoul (Korea, Republic of); Oh, Minyoung; Lee, Sand-Oh; Yu, Eunsil; Ryu Jin-Sook [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    A 53-year-old man with fever of unknown origin underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) as a workup for a fever of unknown origin. On presentation, he complained of fever, chills, and myalgia. The F-18 FDG PET/CT scan showed diffusely increased uptake of the liver with mild hepatomegaly. A liver biopsy then revealed fibrin-ring granulomas typically seen in Q fever. The patient was later serologically diagnosed as having acute Q fever as the titers for C. IgM and IgG were 64:1 and -16:1, respectively. He recovered completely following administration of doxycycline. This indicates that F-18 FDG PET/CT may be helpful for identifying hepatic involvement in Q fever as a cause of fever of unknown origin.

  13. Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A.

    Science.gov (United States)

    Chang, Hyo Jeong; Sinn, Dong Hyun; Cho, Sung Gyun; Oh, Tae Hoon; Jeon, Tae Joo; Shin, Won Chang; Choi, Won Choong

    2014-06-01

    Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA.

  14. (Toxic hepatitis and acute renal failure after inhalation of chloride solvents: report of one case (author's transl))

    Energy Technology Data Exchange (ETDEWEB)

    Teixido Planas, J.; Martinez-Castelao, A.; Romero Gonzalez, R.; Grino Boira, J.; Gonzalez Segura, C.; Caralps Riera, A.

    1981-06-25

    Due to a combination of ingested ethanol and inhaled trichloroethylene (Tri) a 28 year old man developed toxic hepatitis and acute oliguric renal failure, both of which had a favorable evolution. Tri has been described as a cause of hepatic disfunction and acute renal failure due to acute tubular necrosis, although some of the cases described are controversial, because Tri was either contaminated by other dissolvents or could not be proven pure, with the exception of one case. In many there was ethanol ingestion. The Tri inhaled by our patient was found to contain less than 1% of carbon tetrachloride (C-Tchl). This would suggest the C-Tchl to be responsible for the clinical picture although the combination Tri/ethanol cannot be discarded as the causal agent, due to the small amount of contaminant present.

  15. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

    Institute of Scientific and Technical Information of China (English)

    María Jesús Tu(n)ón; Marcelino Alvarez; Jesús M Culebras; Javier González-Gallego

    2009-01-01

    Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by meansof the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

  16. 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.

  17. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

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    J. H. Gillis

    2015-01-01

    Full Text Available Acute sickle hepatic crisis (ASHC has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  18. Parallelogram approach using rat-human In vitro and rat in vivo toxicogenomics predicts acetaminophen-induced hepatotoxicity in humans

    NARCIS (Netherlands)

    Kienhuis, A.S.; Poll, M.C.G. van de; Wortelboer, H.; Herwijnen, M. van; Gottschalk, R.; Jong, C.H.C. de; Boorsma, A.; Paules, R.S.; Kleinjans, J.C.S.; Stierum, R.H.; Delft, J.H.M. van

    2009-01-01

    The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these mo

  19. Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction.

    Science.gov (United States)

    Ahmad, Ghayyor; Sial, Gull Zareen Khan; Ramadori, Pierluigi; Dudas, Jozsef; Batusic, Danko S; Ramadori, Giuliano

    2011-12-01

    Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression.

  20. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008312 Impact of hepatitis B virus infection on the activity of hematopoietic stem cell.SHI Yanmei(石雁梅),et al.Dept Infect Dis,1st Clin Coll,Harbin Med Univ,Harbin 150001.Chin J Infect Dis 2008;26(4):197-201.Objective To study the impact of hepatitis B virus (HBV)infection on the activity of cord hematopoieticstem cells.Methods CD34+cells were isolated from healthy human cord blood by mini MACS.Cells were

  1. Ghrelin reduces liver impairment in a model of concanavalin A-induced acute hepatitis in mice

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    Mao YQ

    2015-09-01

    Full Text Available Yuqing Mao,1 Jianbo Wang,2 Fujun Yu,1 Jian Cheng,1 Huanqing Li,1 Chuanyong Guo,3 Xiaoming Fan11Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai, 2Department of Gastroenterology and Hepatology, The Central Hospital of Lishui City, Wenzhou Medical University, Zhejiang, 3Department of Gastroenterology and Hepatology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of ChinaBackground and aims: Ghrelin is a 28-amino-acid gut hormone that was first discovered as a potent growth hormone secretagogue. Recently, it has been shown to exert a strong anti-inflammatory effect. The purpose of the study reported here was to explore the effect and mechanism of ghrelin on concanavalin (Con A-induced acute hepatitis.Methods: Balb/C mice were divided into four groups: normal control (NC (mice injected with vehicle [saline]; Con A (25 mg/kg; Con A + 10 µg/kg ghrelin; and Con A + 50 µg/kg ghrelin (1 hour before Con A injection. Pro-inflammatory cytokine levels were detected. Protein levels of phosphoinositide 3-kinase (PI3K; phosphorylated Akt (p-Akt; caspase 3, 8, and 9; and microtubule-associated protein 1 light chain 3 (LC3 were also detected. Perifosine (25 mM (an Akt inhibitor was used to investigate whether the protective effect of ghrelin was interrupted by an Akt inhibitor. Protein levels of p-AKT; Bcl-2; Bax; and caspase 3, 8, and 9 were also detected.Results: Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by ghrelin pretreatment in Con A-induced hepatitis. Inflammatory cytokines were significantly reduced by ghrelin pretreatment. Bcl-2; Bax; and caspase 3, 8, and 9 expression were also clearly affected by ghrelin pretreatment, compared with the Con A-treated group. However, the Akt kinase inhibitor reversed the decrease of Bax and caspase 3, 8, 9, and reduced the protein level of p-Akt and Bcl-2. Ghrelin

  2. Efficacy of liver transplantation for acute hepatic failure:a single-center experience

    Institute of Scientific and Technical Information of China (English)

    Xian-Jie Shi; Hong-Bin Xu; Wen-Bin Ji; Yu-Rong Liang; Wei-Dong Duan; Lei He; Ming-Jun Wang; Zhi-Ming Zhao

    2011-01-01

    BACKGROUND: Acute hepatic failure (AHF) is a devastating clinical syndrome with a high mortality rate. The outcome of AHF varies with etiology, but liver transplantation (LT) can significantly improve the prognosis and survival rate of such patients. This study aimed to detect the role of LT and artificial liver support systems (ALSS) for AHF patients and to analyze the etiology and outcome of patients with this disease. METHODS: A retrospective analysis was made of 48 consecutive patients with AHF who fulfilled the Kings College Criteria for LT at our center. We analyzed and compared the etiology, outcome, prognosis, and survival rates of patients between the transplantation (LT) group and the non-transplantation (N-LT) group. RESULTS: AHF was due to viral hepatitis in 25 patients (52.1%; hepatitis B virus in 22), drug or toxic reactions in 14 (29.2%; acetaminophen in 6), Wilson disease in 4 (8.3%), unknown reasons in 3 (6.3%), and miscellaneous conditions in 2 (4.2%). In the LT group, 36 patients (7 underwent living donor LT, and 29 cadaveric LT) had an average model for end-stage liver disease score (MELD) of 35.7. Twenty-eight patients survived with good graft function after a follow-up of 27.3± 4.5 months. During the waiting time, 6 patients were treated with ALSS and 2 of them died during hospitalization. The 30-day, 12-month, and 18-month survival rates were 77.8%, 72.2%, and 66.7%, respectively. In the N-LT group, 12 patients had an average MELD score of 34.5. Four patients were treated with ALSS and all died during hospitalization. The 90-day and 1-year survival rates were only 16.7% and 8.3%, respectively. CONCLUSIONS: Hepatitis is the most prominent cause of AHF at our center. Most patients with AHF, who fulfill the Kings College Criteria for LT, did not survive longer without LT. ALSS did not improve the prognosis of AHF patients, but may extend the waiting time for a donor. Currently, LT is still the most effective way to improve the prognosis

  3. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008449 A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients. MA Jianxin(马建新), et al.Dept Infect Dis, Shanghai Public Health Clin Center, Shanghai 201508. Chin J Intern Med 2008;47(7):574-577. Objective To assess the prevalence of occult HBV infection in HIV-infected patients.

  4. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation

    Science.gov (United States)

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  5. Autochthonous sporadic acute hepatitis E caused by two distinct subgenotype 3b hepatitis E virus strains with only 90% nucleotide identity.

    Science.gov (United States)

    Yamaguchi, Yasuko; Takagi, Hitoshi; Suzuki, Yuhei; Maruhashi, Kyoko; Kosone, Takashi; Kakizaki, Satoru; Sato, Ken; Yamada, Masanobu; Nagashima, Shigeo; Takahashi, Masaharu; Okamoto, Hiroaki

    2017-04-01

    Hepatitis E, which is caused by hepatitis E virus (HEV), is a public health concern in Japan, where the zoonotic food-borne transmission of HEV from domestic pigs and wild boars plays an important role. A 44-year-old Japanese man with autochthonous sporadic acute hepatitis E was admitted with general fatigue and moderate liver dysfunction. In the present study, two distinct HEV strains were recovered from the patient, who had consumed the raw or undercooked pig liver and intestine two or three times per week for 3 months before the disease onset. The recovered HEV strains were segregated into two clusters within subgenotype 3b, the open reading frame (ORF)1 and ORF2 sequences of which each showed ~10% difference, indicating HEV mixed infection. Because most notified patients with clinical HEV infection in Japan are diagnosed based on the detection of IgA-class HEV antibodies and because serum samples from only a limited number of HEV-infected patients are subjected to HEV RNA detection and nucleotide sequencing, it is very likely that patients with HEV mixed infection remain largely overlooked. The identification of sources of autochthonous HEV infection remains an important goal. Continued efforts to trace the sources of acute or chronic autochthonous HEV infection are warranted.

  6. Interstitial nephritis, acute renal failure in a patient with non-fulminant hepatitis A infection.

    Science.gov (United States)

    Vaboe, A L; Leh, S; Forslund, T

    2002-02-01

    This is the first report from Norway of a patient with interstitial nephritis and renal failure due to non-fulminant hepatitis A virus (HAV) infection. HAV infection was confirmed by positive anti-HAV IgM serology. All tests for other virus infections were negative. At admittance serum creatinine (s-Creat) and blood urea nitrogen (BUN) concentration were 539 microlmol/l and 32.6 mmol/l increasing the following days to 890 micromol/l and 39.9 mmol/l, respectively. Nine courses of hemodialysis had to be given. Kidney biopsy specimen showed interstitial edema, lymphocytic cell infiltration and acute tubular injury with normal glomeruli. Examination with immunohistochemistry was negative. In contrast to the findings associated with HBV and HCV infection in which glomerular disease is predominantly found, the HAV infection in our patient was associated with interstitial nephritis and acute tubular necrosis. The prognosis of the renal failure due to HAV infection was good although the recovery was substantially delayed.

  7. Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients.

    Science.gov (United States)

    Riva, E; Maggi, F; Abbruzzese, F; Bellomi, F; Giannelli, G; Picardi, A; Scagnolari, C; Folgori, A; Spada, E; Piccolella, E; Dianzani, F; Antonelli, G

    2009-02-01

    In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

  8. INTERRELATIONS BETWEEN IMMUNOLOGICAL ALTERATIONS AND VIRAL LOAD IN ACUTE HEPATITIS B

    Directory of Open Access Journals (Sweden)

    A. A. Savchenko

    2011-01-01

    Full Text Available Abstract. A group of seventy-six patients with acute viral hepatitis B (HB was under study, in order to evaluate immunological parameters, and ability of blood mononuclear cells to produce cytokines, as dependent on individual viral loads. The immune parameters were less affected in cases of low viral load. Meanwhile, the immune profiles exhibited maximal alterations in the patients with medium and high viral loads. Most expressed changes of immune parameters are found in patients with moderate and high  virus load. Meanwhile, moderate  HB  viral  loads  are  associated  with  higher  functional  activity  of  B-cells  and  lower  NK  numbers, whereas high viral loads correlated with increased amounts of peripheral B cells and higher CD25+ lymphocyte levels. Increased background cytokine synthesis is revealed in mononuclear cells of the patients with acute HB, being, however, suppressed upon additional functional induction. An increased viral load is associated with decreased basal levels of TNFα synthesis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 181-188 

  9. Rifampicin-activated human pregnane X receptor and CYP3A4 induction enhance acetaminophen-induced toxicity.

    Science.gov (United States)

    Cheng, Jie; Ma, Xiaochao; Krausz, Kristopher W; Idle, Jeffrey R; Gonzalez, Frank J

    2009-08-01

    Acetaminophen (APAP) is safe at therapeutic levels but causes hepatotoxicity via N-acetyl-p-benzoquinone imine-induced oxidative stress upon overdose. To determine the effect of human (h) pregnane X receptor (PXR) activation and CYP3A4 induction on APAP-induced hepatotoxicity, mice humanized for PXR and CYP3A4 (TgCYP3A4/hPXR) were treated with APAP and rifampicin. Human PXR activation and CYP3A4 induction enhanced APAP-induced hepatotoxicity as revealed by hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities elevated in serum, and hepatic necrosis after coadministration of rifampicin and APAP, compared with APAP administration alone. In contrast, hPXR mice, wild-type mice, and Pxr-null mice exhibited significantly lower ALT/AST levels compared with TgCYP3A4/hPXR mice after APAP administration. Toxicity was coincident with depletion of hepatic glutathione and increased production of hydrogen peroxide, suggesting increased oxidative stress upon hPXR activation. Moreover, mRNA analysis demonstrated that CYP3A4 and other PXR target genes were significantly induced by rifampicin treatment. Urinary metabolomic analysis indicated that cysteine-APAP and its metabolite S-(5-acetylamino-2-hydroxyphenyl)mercaptopyruvic acid were the major contributors to the toxic phenotype. Quantification of plasma APAP metabolites indicated that the APAP dimer formed coincident with increased oxidative stress. In addition, serum metabolomics revealed reduction of lysophosphatidylcholine in the APAP-treated groups. These findings demonstrated that human PXR is involved in regulation of APAP-induced toxicity through CYP3A4-mediated hepatic metabolism of APAP in the presence of PXR ligands.

  10. Nitric oxide mediates effects of acute, not chronic, naltrexone on LPS-induced hepatic encephalopathy in cirrhotic rats.

    Science.gov (United States)

    Ghiassy, Bentolhoda; Rahimi, Nastaran; Javadi-Paydar, Mehrak; Gharedaghi, Mohammad Hadi; Norouzi-Javidan, Abbas; Dehpour, Ahmad R

    2017-01-01

    Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.

  11. Treatment of acute hepatitis C virus infection with interferon-α 2b and ribavirin: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sunbul Mustafa

    2002-10-01

    Full Text Available Abstract Hepatitis C virus (HCV infection becomes chronic in about 85 % of individuals as demonstrated by the persistence of HCV. It is necesseray to treat acute hepatitis C infection. Interferon-α is generally used for the treatment of acute HCV infection. Case presentation A 55-year-old woman with a history of fatique and icter was diagnosed as acute hepatitis C virus infection. She was treated with interferon-α 2b 3 million unite sc three times in a week and ribavirin 1000 mg daily for 6 months. Within 2 weeks of therapy, the alanine aminotransferase (ALT had became normal. At the end of the 3 months of therapy, HCV RNA was negative and remained negative 6 months after the end of interferon treatment (sustained response. Conclusion This report suggests that interferon-α 2b and ribavirin may have a role in treatment of acute hepatitis C virus infection.

  12. Concurrent acute interstitial pneumonia and pulmonary embolism during treatment with peginterferon alpha-2a and ribavirin in a patient with hepatitis C

    Directory of Open Access Journals (Sweden)

    Hikmet Coban

    2014-01-01

    Full Text Available The case presented is the first patient with concurrent acute interstitial pneumonia and pulmonary embolism associated with combined treatment of peginterferon and ribavirin for hepatitis C.

  13. Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites

    DEFF Research Database (Denmark)

    Toksvang, Linea Natalie; De Pietri, Silvia; Nielsen, Stine N.

    2017-01-01

    BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy...

  14. Serological misdiagnosis of acute liver failure associated with echovirus 25 due to immunological similarities to hepatitis A virus and prozone effect.

    Science.gov (United States)

    Wollersheim, Susan K; Humphries, Romney M; Cherry, James D; Krogstad, Paul

    2015-01-01

    We describe a case of acute liver failure caused by echovirus 25 (E25) in a previously healthy 2-year-old boy. Initial serological studies were consistent with hepatitis A virus (HAV), with prozone phenomenon. The similarity of E25 to HAV may obscure accurate diagnosis in some cases of hepatitis.

  15. A novel multiplex real-time PCR assay for the concurrent detection of hepatitis A, B and C viruses in patients with acute hepatitis.

    Science.gov (United States)

    Park, Yongjung; Kim, Beom Seok; Choi, Kyu Hun; Shin, Dong Ho; Lee, Mi Jung; Cho, Yonggeun; Kim, Hyon-Suk

    2012-01-01

    A novel multiplex real-time PCR assay for concurrent detection of hepatitis viruses was evaluated for its clinical performance in screening patients with acute hepatitis. A total of 648 serum samples were collected from patients with acute symptoms of hepatitis. Concurrent detection of nucleic acids of HAV, HBV and HCV was performed using the Magicplex™ HepaTrio Real-time Detection test. Serum nucleic acid levels of HBV and HCV were also quantified by the Cobas® AmpliPrep/Cobas® TaqMan® (CAP/CTM) HBV and HCV tests. Patients' medical records were also reviewed. Concordance rates between the results from the HepaTrio and the CAP/CTM tests for the detection of HBV and HCV were 94.9% (k = 0.88) and 99.2% (k = 0.98), respectively. The cycle threshold values with the HepaTrio test were also correlated well with the levels of HBV DNA (r = -0.9230) and HCV RNA (r = -0.8458). The sensitivity and specificity of the HepaTrio test were 93.8% and 98.2%, respectively, for detecting HBV infection, and 99.1% and 100.0%, respectively, for HCV infection. For the HepaTrio test, 21 (3.2%) cases were positive for both HBV and HCV. Among the positive cases, 6 (0.9%) were true coinfections. This test also detected 18 (2.8%) HAV positives. The HepaTrio test demonstrated good clinical performance and produced results that agreed well with those of the CAP/CTM assays, especially for the detection of HCV. This assay was also able to detect HAV RNA from anti-HAV IgM-positive individuals. Therefore, this new multiplex PCR assay could be useful for the concurrent detection of the three hepatitis viruses.

  16. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008079 Relationship of HBV genotype and bcp and pc mutations with HBV DNA rebound after lamivudine therapy. SU Minghua(苏明华), et al. Dept Infect Dis Clin Hosp, Guangxi Med Univ, Nanning 530027. World Chin J Digestol 2007;15(33):3507-3513. Objective To investigate the relationship of HBV gene mutations with HBV DNA rebound after lamivudine therapy. Methods Twenty-seven hepatitis B patients with HBV DNA rebound after

  17. Successful management of hepatic mucormycosis in an acute lymphoblastic leukaemia patient: a case report and review of the literature.

    Science.gov (United States)

    Tuysuz, Gulen; Ozdemir, Nihal; Senyuz, Osman Faruk; Emre, Senol; Kantarcioglu, Serda; Adaletli, Ibrahim; Kepil, Nuray; Tutuncu, Cigdem; Celkan, Tiraje

    2014-08-01

    We present a case of hepatic mucormycosis in a 9-year-old boy with acute lymphoblastic leukaemia. Despite long-term use of combined liposomal amphotericin B and posaconazole therapy, the lesion persisted and could only be treated by surgical excision. After surgery, antifungal treatment was continued with posaconazole. On follow-up, the patient had two episodes of ascending cholangitis which were responsive to intravenous antibiotics. He is doing well at the moment in remission for 2.5 years. Mucormycosis was long regarded as a fatal infection with poor prognosis. With early medical and surgical management, survival rates increase. Isolated hepatic mucormycosis is rare and only seven cases were reported in the literature up to now. We wanted to emphasise the role of early surgery in patients with hepatic mucormycosis in view of the literature.

  18. Hepatic abnormal perfusion visible by magnetic resonance imaging in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Wei; tang; Xiao-Ming; Zhang; Zhao-Hua; Zhai; Nan-Lin; Zeng

    2013-01-01

    AIM:to study the prevalence and patterns of hepatic abnormal perfusion(HAP)visible by magnetic resonance imaging(MRI)in acute pancreatitis(AP).METHODS:Enhanced abdominal MRI was performed on 51 patients with AP.these patients were divided into two groups according to the MRI results:those with signs of gallstones,cholecystitis,common bile duct(CBD)stones or dilatation of the CBD on MRI and those without.the prevalence,shape and distribution of HAP in the two groups were analyzed and compared.the severity of AP was graded using the MR severity index(MRSI).the correlation between the MRSI and HAP was then analyzed.RESULTS:Of the 51 patients with AP,32(63%)showed at least one sign of gallbladder and CBD abnormalities on the MR images,while 19(37%)showed no sign of gallbladder or CBD abnormalities.Nineteen patients(37%)had HAP visible in the enhanced images,including strip-,wedge-or patch-shaped HAP distributed in the hepatic tissue adjacent to the gallbladder and left and right liver lobes.there were no significant differences in the prevalence of HAP(χ2=0.305,P=0.581>0.05)or HAP distribution in the liver(χ2=2.181,P=0.536>0.05)between patients with and without gallbladder and CBD abnormalities.there were no significant differences in the MRSI score between patients with and without HAP(t=0.559,P=0.552>0.05).HAP was not correlated with the MRSI score.CONCLUSION:HAP is common in patients with AP and appears strip-,patch-or wedge-shaped on MRI.HAP on MRI cannot be used to indicate the severity of AP.

  19. Serological cross reactivity to CMV and EBV causes problems in the diagnosis of acute hepatitis E virus infection.

    Science.gov (United States)

    Hyams, Catherine; Mabayoje, Diana A; Copping, Ruth; Maranao, Desmond; Patel, Mauli; Labbett, Wendy; Haque, Tanzina; Webster, Daniel P

    2014-03-01

    Hepatitis E virus (HEV) infection is an important public health concern as a major cause of enterically-transmitted hepatitis worldwide. The detectable window of viraemia is narrow, and HEV IgM and IgG rise simultaneously in acute infection. Furthermore, previous investigators have shown HEV IgM false positive reactions occur against EBV, CMV and potentially hepatitis A. A retrospective analysis of HEV serology testing was performed at a London tertiary referral hospital over a 3-year period. A thousand four hundred and twenty three serum samples were tested for HEV serology, with 33 samples HEV IgM positive and 28 HEV IgM equivocal. One hundred and eleven samples were HEV IgG positive but IgM negative suggesting past infection. No patients with HEV IgM positivity had false positive reactions against hepatitis A. A high degree of EBV and CMV cross reactivity was noted, with 33.3% and 24.2% of HEV IgM positive samples also testing positive for EBV and CMV IgM, respectively. HEV RNA was detected in four HEV IgM positive samples, indicating true positivity, although three demonstrated cross reactivity against EBV. Only 13.3% of samples with positive HEV IgM were HEV PCR positive, highlighting a low positive predictive value of serology testing. Overall a high level of HEV, EBV and CMV IgM cross reactivity was demonstrated, indicating that serology is unreliable in the diagnosis of acute viral hepatitis. It is concluded that that the diagnosis of viral hepatitis should be based on clinical features, raised transaminases, serology, and confirmatory PCR testing.

  20. Molecular evolution of GB virus B hepatitis virus during acute resolving and persistent infections in experimentally infected tamarins

    DEFF Research Database (Denmark)

    Takikawa, Shingo; Engle, Ronald E; Faulk, Kristina N

    2010-01-01

    GB virus B (GBV-B) causes acute hepatitis in experimentally infected tamarins. We compared evolutionary features in acute resolving and persistent GBV-B infection. We detected no evidence of evolution in four animals with clearance during weeks 9-12, whereas three animals with clearance during......(-3) substitutions per site year(-1) during weeks 1-52 and 53-104, respectively. Thus, there was a significant decrease in evolution over time, as found for hepatitis C virus. The rate of non-synonymous substitution per non-synonymous site compared with that of synonymous substitution per synonymous site decreased...... over time, suggesting reduction of positive selective pressure. These data demonstrate that prolonged GBV-B infection is associated with viral evolution....

  1. Virological efficacy of combination therapy with corticosteroid and nucleoside analogue for severe acute exacerbation of chronic hepatitis B.

    Science.gov (United States)

    Yasui, S; Fujiwara, K; Nakamura, M; Miyamura, T; Yonemitsu, Y; Mikata, R; Arai, M; Kanda, T; Imazeki, F; Oda, S; Yokosuka, O

    2015-02-01

    The short-term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.

  2. Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis

    Science.gov (United States)

    Carrière, Virginie; Arshad, Muhammad Imran; Le Seyec, Jacques; Lefevre, Benjamin; Farooq, Muhammad; Jan, Aurélien; Manuel, Christelle; Touami-Bernard, Laurence; Lucas-Clerc, Catherine; Genet, Valentine; Gascan, Hugues; Girard, Jean-Philippe; Chalmel, Frédéric; Lamontagne, Lucie; Piquet-Pellorce, Claire

    2017-01-01

    The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver. PMID:28607531

  3. Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis

    Directory of Open Access Journals (Sweden)

    Virginie Carrière

    2017-01-01

    Full Text Available The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO and their wild-type (WT littermates with pathogenic mouse hepatitis virus (L2-MHV3. The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6 at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.

  4. Antibody responses to Hepatitis B and measles-mumps-rubella vaccines in children who received chemotherapy for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Simone Santana Viana

    2012-01-01

    Full Text Available OBJECTIVE: To evaluate viral vaccine antibody levels in children with acute lymphoblastic leukemia after chemotherapy and after vaccine booster doses. METHODS: Antibody levels against hepatitis B, rubella, measles and mumps vaccine antigens were evaluated in 33 children after completing chemotherapy (before and after vaccine booster doses and the results were compared to the data of 33 healthy children matched for gender, age and social class. RESULTS: After chemotherapy, 75.9%, 67.9%, 59.3% and 51.7% of the patients showed low antibody titers that would be unlikely to protect against exposure to measles, rubella, hepatitis B and mumps, respectively. After receiving a vaccine booster dose for these antigens the patients had high antibody levels consistent with potential protection against measles, mumps and hepatitis B, but not against rubella. CONCLUSION: Extra doses of measles-mumps-rubella plus hepatitis B vaccines are recommended in acute lymphoblastic leukemia patients submitted to treatment after hematologic recovery. After this, viral vaccine antibody levels should be verified to define the individual's protective status.

  5. Reduced SHARPIN and LUBAC Formation May Contribute to CCl4- or Acetaminophen-Induced Liver Cirrhosis in Mice

    Directory of Open Access Journals (Sweden)

    Takeshi Yamamotoya

    2017-02-01

    Full Text Available Linear ubiquitin chain assembly complex (LUBAC, composed of SHARPIN (SHANK-associated RH domain-interacting protein, HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1, and HOIP (HOIL-1L interacting protein, forms linear ubiquitin on nuclear factor-κB (NF-κB essential modulator (NEMO and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl4 or acetaminophen (APAP, both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein. Seven days after this transduction, without additional inflammatory stimuli, substantial inflammation and fibrosis with enhanced hepatocyte apoptosis occurred in the livers. A similar but more severe phenotype was observed with suppression of HOIP, which is responsible for the E3 ligase activity of LUBAC. Furthermore, in good agreement with these in vivo results, transduction of Hepa1-6 hepatoma cells with SHARPIN, HOIL-1L, or HOIP shRNA adenovirus induced apoptosis of these cells in response to tumor necrosis factor-α (TNFα stimulation. Thus, LUBAC is essential for the survival of hepatocytes, and it is likely that reduction of LUBAC is a factor promoting hepatocyte death in addition to the direct effect of drug toxicity.

  6. Reduced SHARPIN and LUBAC Formation May Contribute to CCl₄- or Acetaminophen-Induced Liver Cirrhosis in Mice.

    Science.gov (United States)

    Yamamotoya, Takeshi; Nakatsu, Yusuke; Matsunaga, Yasuka; Fukushima, Toshiaki; Yamazaki, Hiroki; Kaneko, Sunao; Fujishiro, Midori; Kikuchi, Takako; Kushiyama, Akifumi; Tokunaga, Fuminori; Asano, Tomoichiro; Sakoda, Hideyuki

    2017-02-04

    Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl₄) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein. Seven days after this transduction, without additional inflammatory stimuli, substantial inflammation and fibrosis with enhanced hepatocyte apoptosis occurred in the livers. A similar but more severe phenotype was observed with suppression of HOIP, which is responsible for the E3 ligase activity of LUBAC. Furthermore, in good agreement with these in vivo results, transduction of Hepa1-6 hepatoma cells with SHARPIN, HOIL-1L, or HOIP shRNA adenovirus induced apoptosis of these cells in response to tumor necrosis factor-α (TNFα) stimulation. Thus, LUBAC is essential for the survival of hepatocytes, and it is likely that reduction of LUBAC is a factor promoting hepatocyte death in addition to the direct effect of drug toxicity.

  7. Wnt/β-Catenin Signaling Drives Thioacetamide-Mediated Heteroprotection Against Acetaminophen-Induced Lethal Liver Injury

    Science.gov (United States)

    Dadhania, Vivekkumar P.; Bhushan, Bharat

    2017-01-01

    Preplacement of compensatory tissue repair (CTR) by exposure to a nonlethal dose of a toxicant protects animals against a lethal dose of another toxicant. Although CTR is known to heteroprotect, the underlying molecular mechanisms are not completely known. Here, we investigated the mechanisms of heteroprotection using thioacetamide (TA): acetaminophen (APAP) heteroprotection model. Male Swiss Webster mice received a low dose of TA or distilled water (DW) vehicle 24 hours prior to a lethal dose of APAP. Liver injury, tissue repair, and promitogenic signaling were studied over a time course of 24 hours after APAP overdose to the TA- and DW-primed mice (TA + APAP and DW + APAP, respectively). Thioacetamide pretreatment afforded 100% protection against APAP overdose compared to 100% lethality in the DW + APAP-treated mice. Although hepatic Cyp2e1 was similar at the time of APAP administration, immediate activation of hepatic c-Jun N-terminal kinases (JNK) was observed in the TA + APAP-treated mice compared to its delayed activation in the DW + APAP group. In contrast to the DW + APAP group, the TA + APAP-treated mice exhibited extensive CTR, which was secondary to the timely activation of Wnt/β-catenin pathway. Our data indicate that rapid activation and appropriate termination of Wnt/β-catenin signaling and modulation of JNK activity underlie TA + APAP heteroprotection. PMID:28210203

  8. Reduced SHARPIN and LUBAC Formation May Contribute to CCl4- or Acetaminophen-Induced Liver Cirrhosis in Mice

    Science.gov (United States)

    Yamamotoya, Takeshi; Nakatsu, Yusuke; Matsunaga, Yasuka; Fukushima, Toshiaki; Yamazaki, Hiroki; Kaneko, Sunao; Fujishiro, Midori; Kikuchi, Takako; Kushiyama, Akifumi; Tokunaga, Fuminori; Asano, Tomoichiro; Sakoda, Hideyuki

    2017-01-01

    Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl4) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein. Seven days after this transduction, without additional inflammatory stimuli, substantial inflammation and fibrosis with enhanced hepatocyte apoptosis occurred in the livers. A similar but more severe phenotype was observed with suppression of HOIP, which is responsible for the E3 ligase activity of LUBAC. Furthermore, in good agreement with these in vivo results, transduction of Hepa1-6 hepatoma cells with SHARPIN, HOIL-1L, or HOIP shRNA adenovirus induced apoptosis of these cells in response to tumor necrosis factor-α (TNFα) stimulation. Thus, LUBAC is essential for the survival of hepatocytes, and it is likely that reduction of LUBAC is a factor promoting hepatocyte death in addition to the direct effect of drug toxicity. PMID:28165393

  9. [Etiology and epidemiology of 547 episodes of acute viral hepatitis diagnosed in adults in a general hospital (1983-1994)].

    Science.gov (United States)

    Rodriguez, M; Martinez, A; Sala, P; Pérez, R; Linares, A; Sánchez-Lombraña, J L; Rodrigo, L

    1996-01-01

    The etiology and epidemiology of 547 consecutive episodes of acute viral hepatitis in adults and diagnosed in a general hospital over 12 years (1983-1994) were prospectively analyzed as were the changes observed during the two halves of the study period. Of the 547 episodes, 25.4% were of type A, 41.1% type B, 21.9% type C, 6.6% non A, non B, non C, 2.4% type D, 1.1% by cytomegalovirus and 1.4% by the Epstein-Barr virus. The proportion of hepatitis A increased from 21.5% from 1983-1988 to 34.1% from 1989-1994 (p = 0.002), while hepatitis C decreased from 24.9% to 15.3% (p = 0.01) during the same periods. The proportion of hepatitis B observed in intravenous drug addicts fell from 56.1% in the first period to 39.3% in the second period (p = 0.03), while sexually transmitted hepatitis B rose from 7.3% to 22.9% (p = 0.002). A decrease was observed in the cases of hepatitis C in both periods in the intravenous drug addict cases (60.6% vs. 34.6%; p = 0.03) with an increase being observed in the C virus transmitted by unapparent mechanisms (2.1% vs. 23.1%; p = 0.001). These results suggest that modifications may currently be observed in the epidemiology of the viral hepatitis in Spain and that these trends should be taken into account when planning preventive strategies.

  10. Serial measurement of Doppler hepatic hemodynamic parameters for the diagnosis of acute rejection after live donor liver transplantation.

    Science.gov (United States)

    Sugimoto, Hiroyuki; Kato, Koichi; Hirota, Masashi; Takeda, Shin; Kamei, Hideya; Nakamura, Taro; Kiuchi, Tetsuya; Nakao, Akimasa

    2009-09-01

    To elucidate the role of Doppler hepatic hemodynamic parameters as surrogate markers of acute rejection (AR) after live donor liver transplantation (LDLT), serial Doppler measurements were prospectively performed during the first 2 weeks after LDLT to compare the longitudinal hepatic hemodynamic changes between patients with histologically proven AR and patients without histologically proven AR. Forty-six patients that had undergone adult-to-adult LDLT using a right lobe graft were enrolled in this study. The portal venous maximum velocity (PVV; cm/second), portal venous flow volume, hepatic arterial peak systolic velocity, hepatic arterial pulsatility index, hepatic venous maximum velocity, hepatic venous pulsatility index, and splenic arterial pulsatility index were measured. Fourteen patients were diagnosed by biopsy to have clinically relevant AR. Markedly increased PVV was seen soon after surgery and gradually decreased in both patients with clinically relevant AR and patients without clinically relevant AR. This serial change of decreasing PVV was significantly greater in patients with clinically relevant AR (P patients with clinically relevant AR was significantly lower than that in patients without clinically relevant AR (PVV on postoperative day 6: 35.6 +/- 21.3 versus 58.3 +/- 27.1 cm/second, respectively, P = 0.0080). A PVV cutoff value of 20.2 cm/second demonstrated the best accuracy for predicting clinically relevant AR. The sensitivity and specificity for predicting clinically relevant AR were 92.9% and 87.1%, respectively. The area under the curve was 0.94. In conclusion, serial Doppler measurement of hepatic parameters in LDLT is useful for the diagnosis of clinically relevant AR. Clinically relevant AR should therefore be suspected when a marked unexpected decrease in the PVV is observed.

  11. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina.

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    María Belén Rodrigo

    Full Text Available Hepatitis B virus (HBV is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%, A2 (18.2%, F4 (18.2% and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases.

  12. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina

    Science.gov (United States)

    Rodrigo, María Belén; Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; González López Ledesma, María Mora; Perez, Paula Soledad; Bouzas, María Belén; Galdame, Omar; Marciano, Sebastián; Fainboim, Hugo; Flichman, Diego Martín; Campos, Rodolfo Héctor

    2016-01-01

    Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases. PMID:27433800

  13. Temporal association of acute hepatitis A and Plasmodium falciparum malaria in children.

    Directory of Open Access Journals (Sweden)

    Peter Klein Klouwenberg

    Full Text Available BACKGROUND: In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists. MATERIALS AND METHODS: We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period. DISCUSSION: Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81-3.1 infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14-0.50 infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively, largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation. CONCLUSION: The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.

  14. Kupffer cells facilitate the acute effects of leptin on hepatic lipid metabolism.

    Science.gov (United States)

    Metlakunta, Anantha; Huang, Wan; Stefanovic-Racic, Maja; Dedousis, Nikolaos; Sipula, Ian; O'Doherty, Robert M

    2017-01-01

    Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the metabolic effects of leptin were maintained in mice lacking ObR in hepatocytes. Notably, liver TG were elevated in both lean and obese myeloid cell ObR, but the degree of obesity and insulin resistance induced by a high-fat diet was similar to control mice. In isolated primary hepatocytes (HEP), leptin had no effects on HEP lipid metabolism and only weakly stimulated PI3K. However, the coculture of KC with HEP restored leptin action on HEP fatty acid metabolism and stimulation of HEP PI3K. Notably, leptin stimulated the release from KC of a number of cytokines. However, the exposure of HEP to these cytokines individually [granulocyte macrophage colony-stimulating factor, IL-1α, IL-1β, IL-6, IL-10, and IL-18] or in combination had no effects on HEP lipid metabolism. Together, these data demonstrate a role for liver mononuclear cells in the regulation of liver lipid metabolism by leptin. Copyright © 2017 the American Physiological Society.

  15. Biochemical mechanism underlying hypertriglyceridemia and hepatic steatosis/hepatomegaly induced by acute schisandrin B treatment in mice.

    Science.gov (United States)

    Zhang, Yi; Zhao, Jing; Zhou, Shu-Feng; Yu, Zhi-Ling; Wang, Xiao-Yan; Zhu, Pei-Li; Chu, Zhu-Sheng; Pan, Si-Yuan; Xie, Ming; Ko, Kam-Ming

    2017-01-13

    It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. Male ICR mice were given a single oral dose of Sch B (0.25-2 g/kg). Sch B-induced changes in serum levels of biomarkers, such as TG, total cholesterol (TC), apolipoprotein B48 (ApoB 48), very-low-density lipoprotein (VLDL), non-esterified fatty acid (NEFA) and hepatic growth factor (HGF), as well as hepatic lipids and mass, epididymal adipose tissue (EAT) and adipocyte size, and histological changes of the liver and EAT were examined over a period of 12-120 h after Sch B treatment. Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h, respectively, after Sch B administration. Sch B treatment elevated serum ApoB 48 level (up to 12%), a marker of exogenous TG, but not VLDL, as compared with the vehicle treatment. Treatment with Sch B caused a time-/dose-dependent reduction in EAT index (up to 39%) and adipocyte size (up to 67%) and elevation in serum NEFA level (up to 55%). Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs. the vehicle control) and lipid positive staining area (up to 17.5 × 10(3) μm(2)) in liver tissue. Hepatic index and serum HGF levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively. In addition, ultrastructural changes, such as increase in size and disruption of cristae, in hepatic mitochondria were observed in Sch B-treated mice. Our findings suggest that exogenous sources of TG and the breakdown of fat storage in the body contribute to Sch B

  16. Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

    Science.gov (United States)

    Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

    2011-07-05

    Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

  17. [Coping strategies used by the family of a patient with acute fulminant hepatitis].

    Science.gov (United States)

    Iriarte Cerdán, Laura; Ruiz de Galarreta, Leire Martínez; Olano Lizarraga, Maddi; García Vivar, Cristina

    2012-04-01

    In the holistic care to the patient, the family should be an important part because its members are also affected by the situation. Therefore, nursing work should be directed to both the individual and his environment, being of great help to identify family's needs in order to meet their specific needs accurately. Also in the process of recovery the family goes through several stages of coping, each of them have its own characteristics and nurses' interventions should be adapted to them. The aim of this paper is to evidence the importance of caring for the family, identifying the stages of coping, recognizing their needs and identifying relevant care. For this, a clinical case of a family with a relative hospitalised in an intensive care unit because of an acute fulminant hepatitis was developed. The instruments used to carry out the analysis of the case are: family's needs described by Leske et al., coping stages identified by Kubler-Ross, and ways of coping scale developed by Lazarus and Folkman. Nurses have a relevant role due to their close contact with people, this helps to become a factor which facilitates the interaction of patient and family within the hospital environment. A holistic approach of nursing care involves assessing the needs of families to develop strategies for effective interventions.

  18. Acute hepatitis C virus infection in a nurse trainee following a needlestick injury

    Science.gov (United States)

    Scaggiante, Renzo; Chemello, Liliana; Rinaldi, Roberto; Bartolucci, Giovanni Battista; Trevisan, Andrea

    2013-01-01

    Hepatitis C virus (HCV) infection after biological accident (needlestick injury) is a rare event. This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padua University Hospital. The student nurse was injured on the second finger of the right hand when recapping a 23-gauge needle after taking a blood sample. The patient who was the source was a 72-year-old female with weakly positive anti-HCV test results. Three months after the injury, at the second step of follow-up, a relevant increase in transaminases with a low viral replication activity (350 IU/mL) was observed in the student, indicating HCV infection. The patient tested positive for the same genotype (1b) of HCV as the injured student. A rapid decline in transaminases, which was not accompanied by viral clearance, and persistently positive HCV-RNA was described 1 mo later. Six months after testing positive for HCV, the student was treated with pegylated interferon plus ribavirin for 24 wk. A rapid virological response was observed after 4 wk of treatment, and a sustained virological response (SVR) was evident 6 mo after therapy withdrawal, confirming that the patient was definitively cured. Despite the favourable IL28B gene (rs12979860) CC- polymorphism observed in the patient, which is usually predictive of a spontaneous clearance and SVR, spontaneous viral clearance did not take place; however, infection with this genotype was promising for a sustained virological response after therapy. PMID:23382640

  19. [Acute outbreak of hepatitis C in human immunodeficiency virus-infected patients].

    Science.gov (United States)

    Martínez-Rebollar, Maria; Mallolas, Josep; Pérez, Iñaki; González-Cordón, Ana; Loncà, Montserrat; Torres, Berta; Rojas, Jhon-Fredy; Monteiro, Polyana; Blanco, José-Luis; Martínez, Esteban; Gatell, José-María; Laguno, Montserrat

    2015