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Sample records for acute alcoholic hepatitis

  1. Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis

    PubMed Central

    Hunter, Jonathan Michael; Chan, Julian; Reid, Angeline Louise; Tan, Chistopher

    2013-01-01

    A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcohol-related liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms. PMID:23355576

  2. Hemolysis in Acute Alcoholic Hepatitis: Zieve's Syndrome

    PubMed Central

    Sitrin, Michael

    2015-01-01

    A 45-year-old man presented with acute alcoholic hepatitis, jaundice, and anemia on admission. There was no history of bleeding or any evidence of gastrointestinal blood loss. Lab studies revealed hemolysis as the cause of anemia. The patient was diagnosed with Zieve's syndrome and managed with supportive measures. He recovered well and was discharged to a detoxification unit in a stable condition. Zieve's syndrome has been described in literature, mostly in non-English language case studies, but is largely under-recognized and under-reported. Diagnosis should be made quickly to avoid unnecessary invasive diagnostic interventions. PMID:26203455

  3. Immune dysfunction in acute alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Collins, Peter L

    2015-01-01

    Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. PMID:26576079

  4. Pharmacotherapy of acute alcoholic hepatitis in clinical practice

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Rouabhia, Samir; Addolorato, Giovanni

    2014-01-01

    Severe alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol. The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features, and several scoring systems. Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence. Liver transplantation is a possible therapeutic option for severe AH. Among the anti-craving medications able to improve abstinence rate, baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage. PMID:24605014

  5. Alcoholic hepatitis

    PubMed Central

    Jewell, L. D.; Medline, A.; Medline, N. M.

    1971-01-01

    Clinical and pathological data from four cases of fatal non-cirrhotic alcoholic hepatitis are presented. The patients were relatively young but had a long history of excessive alcohol intake, and the disease had an acute onset which progressed inexorably to death in hepatic and renal failure. At autopsy the livers were enlarged but non-cirrhotic. The important histological criteria for the diagnosis of alcoholic hepatitis are a panlobular polymorphonuclear inflammatory cell infiltrate, the presence of Mallory material (alcoholic hyaline) and fine fibrosis surrounding small groups of liver cells. The latter finding may be more marked in the centrolobular zone and result in the picture of central hyaline sclerosis. ImagesFig. 1AFig. 1BFig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:4106422

  6. [Alcoholic hepatitis].

    PubMed

    Radchenko, V G; Prikhod'ko, E M

    2012-01-01

    The aim of the study was to evaluate Kholit efficiency in complex treatment of alcoholic hepatitis. 72 patients with proved chronic alcoholic hepatitis were examined. 37 of them underwent complex treatment including Kholit. Kholit in complex treatment of patients with chronic alcoholic hepatitis was shown to promote improvement of the general patient's state, disappearance of objective signs of the disease, normalization of laboratory and instrumental data. PMID:23402199

  7. Alcohol and Hepatitis C

    MedlinePlus

    ... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one of the ...

  8. Update on Alcoholic Hepatitis

    PubMed Central

    Torok, Natalie J.

    2015-01-01

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%–50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies. PMID:26540078

  9. Acute Hepatitis.

    PubMed

    Proujansky; Vinton

    1995-10-01

    The acute onset of hepatitis may occur in adolescents as a result of hepatic damage from infectious agents, drugs, or toxins, or it may be the initial presentation of a chronic autoimmune or metabolic liver disease. The authors characterize the clinical features of each of these disorders emphasizing recognition and diagnosis. PMID:10358327

  10. Alcohol and Viral Hepatitis

    PubMed Central

    Dolganiuc, Angela

    2015-01-01

    Both alcohol abuse and infection with hepatitis viruses can lead to liver disease, including chronic hepatitis. Alcohol and hepatitis viruses have synergistic effects in the development of liver disease. Some of these involve the cellular membranes and particularly their functionally active domains, termed lipid rafts, which contain many proteins with essential roles in signaling and other processes. These lipid rafts play a central role in the lifecycles of hepatitis viruses. Alcohol’s actions at the lipid rafts may contribute to the synergistic harmful effects of alcohol and hepatitis viruses on the liver and the pathogenesis of liver disease. PMID:26695752

  11. Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

    PubMed Central

    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH. PMID:25461442

  12. Early liver transplantation for patients with acute alcoholic hepatitis: public views and the effects on organ donation.

    PubMed

    Stroh, G; Rosell, T; Dong, F; Forster, J

    2015-06-01

    Patients with severe acute alcoholic hepatitis may not survive to fulfill the standard 6 months of abstinence and counseling prior to transplantation. A prospective study demonstrated that early liver transplantation in such patients improved 2 year survival from 23% to 71% and only 3 of 26 patients returned to drinking after 1140 days; graft function was unaffected. Nonetheless, this treatment protocol may raise public concerns and affect organ donation rates. A total of 503 participants took a survey made available at an online crowdsourcing marketplace. The survey measured attitudes on liver transplantation generally and early transplantation for this patient population, in addition to measuring responses to nine vignettes describing fictional candidates. The majority of respondents (81.5%, n = 410) was at least neutral toward early transplantation for these patients; only a minority (26.3%) indicated that transplantation in any vignette would make them hesitant to donate their organs. Middle-aged patients with good social support and financial stability were viewed most favorably (p < 0.001). Age was considered the most important selection factor and financial stability the least important factor (each p < 0.001). Results indicate early transplantation for carefully selected patients with acute alcoholic hepatitis may not be as controversial to the public as previously thought. PMID:25707427

  13. Acute Q fever presenting as fever of unknown origin with rapidly progressive hepatic failure in a patient with alcoholism.

    PubMed

    Lin, Po-Han; Lo, Yi-Chun; Chiang, Fu-Tien; Wang, Jiun-Ling; Jeng, Yung-Ming; Fang, Chi-Tai; Chang, Shan-Chwen

    2008-11-01

    We report a case of fulminant acute Q fever presenting as fever of unknown origin with rapidly progressive hepatic failure in a patient with alcoholism. A 51-year-old electrician, who was a habitual drinker, presented with a 2-week history of intermittent high fever, acute hepatomegaly and rapidly progressive jaundice after being accidentally exposed to dust from bird nests when he was repairing electrical equipment and circuitry at an abandoned factory in Taipei County. Ascites and prolonged prothrombin time were noted at admission. Transjugular liver biopsy and bone marrow biopsy found multiple small fibrinoid-ring granulomas in liver parenchyma and bone marrow. Doxycycline therapy was empirically started. The fever gradually subsided over a 2-week period, along with the recovery of liver function. The diagnosis of acute Q fever was confirmed by high titers of antibodies against Coxiella burnetii (phase I IgM 1:160 and IgG 1:2560, phase II IgM > 1:320 and IgG 1:5120) and a four-fold elevation of phase II IgG titer in the paired serum. The experience of this case shows that the possibility of Q fever should not be overlooked in patients who have an unexplained febrile illness and severe liver function impairment following exposure to a contaminated environment in Taiwan. PMID:18971160

  14. Alcoholic hepatitis: Prognosis and treatment.

    PubMed

    Casanova, Jennifer; Bataller, Ramón

    2014-04-01

    Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and is the most severe form of alcoholic liver disease. AH occurs in patients with heavy alcohol abuse and underlying liver disease. In its severe form, AH carries a poor short-term prognosis. Although the existence of AH can be strongly suspected based on clinical and biochemical criteria, a definitive diagnosis requires a liver biopsy. There is a clear need to develop non-invasive markers for these patients. The prognosis of patients with AH can be established by different score systems (Maddrey's DF, ABIC, MELD and Glasgow). Recently, a histological scoring system able to estimate prognosis has been developed (Alcoholic Hepatitis Histological Score - AHHS). The management of patients with AH has changed little in the last few decades. In patients with severe form of AH, prednisolone and pentoxifylline are the first line therapy. Unfortunately, many patients do not respond and novel targeted therapies are urgently needed. Current research is aimed at identifying the main disease drivers and to develop animal models of true AH. For non-responders to medical therapy, the only curative option is to perform a salvage liver transplantation. This particular indication of liver transplantation is currently under debate and prospective studies should evaluate the specific patient evaluation and selection criteria. PMID:24656653

  15. The hepatic-arterial/portal-venous scintiangiogram in alcoholic hepatitis

    SciTech Connect

    Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.

    1984-01-01

    This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.

  16. Acute alcohol intoxication.

    PubMed

    Vonghia, Luisa; Leggio, Lorenzo; Ferrulli, Anna; Bertini, Marco; Gasbarrini, Giovanni; Addolorato, Giovanni

    2008-12-01

    Acute alcohol intoxication is a clinically harmful condition that usually follows the ingestion of a large amount of alcohol. Clinical manifestations are heterogeneous and involve different organs and apparatuses, with behavioral, cardiac, gastrointestinal, pulmonary, neurological, and metabolic effects. The management of an intoxicated patient occurs mainly in the emergency department and is aimed at stabilizing the clinical condition of the patient, depending on his/her clinical presentation. One specific drug that is useful in the treatment of acute alcohol intoxication is metadoxine, which is able to accelerate ethanol excretion. In patients presenting an acute alcohol intoxication, alcohol-related disorders should be detected so that the patient can be directed to an alcohol treatment unit, where a personalized, specific treatment can be established. PMID:19046719

  17. Hyperbilirubinaemia and haemolytic anaemia in acute alcoholic hepatitis: there's oil in them thar veins

    PubMed Central

    Hashmi, Salman; Allison, Michael G; McCurdy, Michael T; Reed, Robert M

    2014-01-01

    A Caucasian woman in her late 30s was evaluated after a period of binge drinking and found to have hyperbilirubinaemia for which she was referred for consideration of cholecystectomy. After exclusion of other possibilities, Zieve's syndrome was diagnosed. This is a condition of hyperbilirubinaemia, Coombs’ negative haemolytic anaemia and hyperlipidaemia associated with alcoholism. Abstinence from alcohol remains the only known effective treatment, and appreciation of the entity can prevent unnecessary biliary procedures. The patient improved with supportive measures and was discharged in stable condition. PMID:24748143

  18. [Pathogenesis of alcoholic chronic hepatitis].

    PubMed

    Hayashi, Nobuhiko; Saito, Takashi; Kakuda, Masahiro; Matsue, Yasuhiro; Minato, Takashiro; Fukumura, Atsushi; Ozaki, Kazuaki; Tsuchisima, Mutsumi; Tsutsumi, Mikihiro

    2014-10-01

    In 1983, Nei et al. reported that alcoholic chronic hepatitis (ACH)(chronic hepatitis induced tal area. Recently, the number of alcoholics patients diagnosed with ACH has been increased In this review, we discussed the characteristics of liver histopathology and blood chemistry of ACH patients. In ACH, pericellular fibrosis, ballooned hepatocytes and/or bridging fibrosis, and infiltration of mononuclear lymphocytes is decreased after 6 to 8 weeks of abstinence from results suggest that ACH could be one type of alcoholic liver disease. The precise mechanism by alcohol) as one type of alcoholic liver disease. Since then, it has been discussed whether alcohol abuse, suggesting that alcohol may play a role in the infiltration of mononuclear lym ACH is one type of alcoholic liver disease, because there could be infection of unknown hepatitis virus in alcoholics and it is not clear why mononuclear lymphocytes infiltrate into the porphocytes in portal region. After abstinence of alcohol, serum levels of AST, ALT, and γ-GTP in patients with ACH returned to normal as in other types of alcoholic liver disease such as alcoholic fatty liver, alcoholic fibrosis, alcoholic hepatitis and alcoholic liver cirrhosis. These results suggest that ACH could be one type of alcoholic liver disease. The precise mechanism of the infiltration of mononuclear lymphocytes into portal areas of ACH patients is not known. We propose that the reason for the infiltration of natural killer (T) cells into portal areas could be due to the influx of endotoxin into portal vein resulting from the increased permeability of gut induced by alcohol. PMID:25651616

  19. Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease.

    PubMed

    Wilkin, Richard J W; Lalor, Patricia F; Parker, Richard; Newsome, Philip N

    2016-04-01

    Alcohol-induced liver damage is a major burden for most societies, and murine studies can provide a means to better understand its pathogenesis and test new therapies. However, there are many models reported with widely differing phenotypes, not all of which fully regenerate the spectrum of human disease. Thus, it is important to understand the implications of these variations to efficiently model human disease. This review critically appraises key articles in the field, detailing the spectrum of liver damage seen in different models, and how they relate to the phenotype of disease seen in patients. A range of different methods of alcohol administration have been studied, ranging from ad libitum consumption of alcohol and water to modified diets (eg, Lieber deCarli liquid diet). Other feeding regimens have taken more invasive routes using intragastric feeding tubes to infuse alcohol directly into the stomach. Notably, models using wild-type mice generally produce a milder phenotype of liver damage than those using genetically modified mice, with the exception of the chronic binge-feeding model. We recommend panels of tests for consideration to standardize end points for the evaluation of the severity of liver damage-key for comparison of models of injury, testing of new therapies, and subsequent translation of findings into clinical practice. PMID:26835538

  20. Advances in alcoholic liver disease: An update on alcoholic hepatitis

    PubMed Central

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory’s hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey’s discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline. PMID:26576078

  1. The hepatoprotective effect of aqueous extracts of Penthorum chinense Pursh against acute alcohol-induced liver injury is associated with ameliorating hepatic steatosis and reducing oxidative stress.

    PubMed

    Cao, Yi-Wei; Jiang, Yun; Zhang, Da-Yong; Zhang, Xiao-Jing; Hu, Yuan-Jia; Li, Peng; Su, Huanxing; Wan, Jian-Bo

    2015-05-01

    The aim of the present study was to evaluate the effects of Penthorum chinense Pursh (PCP), a health food and folk medicine, against acute alcohol-induced liver injury and further to elucidate its probable mechanisms. Male C57BL/6 mice were treated with an aqueous extract of PCP (5.2 and 10.3 g per kg BW) once daily for 7 consecutive days prior to ethanol gavage (4.7 g kg(-1)) every 12 h for a total of three doses. Pretreatment with PCP significantly decreased the elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic triglyceride after the last ethanol administration. PCP suppressed the elevation of the malondialdehyde (MDA) level, restored the glutathione (GSH) level and enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in both the serum and liver, which were associated with the inhibition of hepatic cytochrome P450 2E1 (CYP2E1). In addition, alcohol exposure markedly induced the lipolysis of white adipose tissue (WAT) through up-regulating protein expressions of adipose triglyceride lipase (ATGL) and phosphorylation of hormone-sensitive lipase (p-HSL), and enhancing the fatty acid uptake capacity in the liver by elevated hepatic CD36 expression, which were attenuated by PCP treatment. These data demonstrated that pre-treatment with PCP protected against acute ethanol-induced liver injury, possibly by reducing CYP2E1-dependent oxidative stress and ameliorating dysfunctional WAT derived-fatty acid influx to the liver. Our findings suggest that PCP might be a promising agent for the prevention of acute alcohol-induced liver injury. PMID:25820653

  2. [Some histological criteria for the renal and hepatic lesions in the case of death from acute intoxication with ethyl alcohol].

    PubMed

    Os'minkin, V A

    2015-01-01

    The objective of the present study was to evaluate the results of the microscopic studies of acute intoxication with ethyl alcohol at the territory of the Udmurtian Republic during the period from 2003 till 2013. A total of 5941 cases of death caused by acute intoxication with ethyl alcohol were documented among both men and women, largely able-bodied ones. Concentration of ethyl alcohol in their blood corresponded to the one known to result in severe or lethal intoxication, The forensic histological study of the available tissue samples gave evidence of vascular disturbances, enhanced permeability of the vascular walls, dystrophic changes in the internal organs, the signs of necronephrosis, and concomitant disorders. Epithelium of renal tubules obtained from 0.4% of the corpses contained the pigment particles of different structure and colour; other pathological changes included cholestasis, necrosis of hepatocytes, various lesions and injuries. Similar alterations were identified in the detoxificating organs of the subjects who had died from causes other than acute intoxication with ethyl alcohol. These findings suggest disturbances of pigment metabolism and make it possible to elucidate the peculiar features of patho- and tanatogenesis. PMID:25874313

  3. Acute hepatic failure in children.

    PubMed Central

    Riely, C. A.

    1984-01-01

    Many diseases may present as acute hepatic failure in the pediatric age group, including viral hepatitis A and B, adverse drug reactions, both toxic and "hepatitic," and inherited metabolic disorders such as tyrosinemia, alpha 1 antitrypsin deficiency, and Wilson's disease. Management is primarily supportive, with care taken to anticipate the known complications of hepatic failure. Few "curative" therapies are known, although attempts at stimulating hepatic regeneration may be helpful. Images FIG. 1 FIG. 3 FIG. 4 PMID:6433587

  4. Treatment of Severe Alcoholic Hepatitis.

    PubMed

    Thursz, Mark; Morgan, Timothy R

    2016-06-01

    Alcoholic hepatitis (AH) is a syndrome of jaundice and liver failure that occurs in a minority of heavy consumers of alcohol. The diagnosis usually is based on a history of heavy alcohol use, findings from blood tests, and exclusion of other liver diseases by blood and imaging analyses. Liver biopsy specimens, usually collected via the transjugular route, should be analyzed to confirm a diagnosis of AH in patients with an atypical history or presentation. The optimal treatment for patients with severe AH is prednisolone, possibly in combination with N-acetyl cysteine. At present, only short-term increases in survival can be expected-no treatment has been found to increase patient survival beyond 3 months. Abstinence is essential for long-term survival. New treatment options, including liver transplantation, are being tested in trials and results eagerly are awaited. PMID:26948886

  5. Acute hepatitis after amiodarone infusion

    PubMed Central

    Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco

    2015-01-01

    Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients. PMID:26488027

  6. Alcoholic hepatitis: A comprehensive review of pathogenesis and treatment

    PubMed Central

    Chayanupatkul, Maneerat; Liangpunsakul, Suthat

    2014-01-01

    Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH. PMID:24876748

  7. New treatment options for alcoholic hepatitis.

    PubMed

    Shasthry, Saggere Muralikrishna; Sarin, Shiv Kumar

    2016-04-21

    The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using "Omics" platforms, newer options for patients with alcoholic hepatitis are expected soon. PMID:27099434

  8. [The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury].

    PubMed

    Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li

    2015-02-25

    In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H₂O₂) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H₂O₂and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury. PMID:25672632

  9. Therapeutic Strategies for the Treatment of Alcoholic Hepatitis.

    PubMed

    Singal, Ashwani K; Shah, Vijay H

    2016-02-01

    Acute alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active heavy alcohol use. Presenting with acute or chronic liver failure, a severe episode has a potential for 30 to 40% mortality at 1 month from presentation, if not recognized and left untreated. Alcoholic hepatitis patients need supportive therapy for abstinence and nutritional supplementation for those patients with markedly reduced caloric intake. Results of the recently published STOPAH (Steroids or Pentoxifylline for Alcoholic Hepatitis) Study showed only a benefit of corticosteroids on short-term mortality without any benefit of pentoxifylline. Neither of these two drugs impacts medium- and long-term mortality, which is mainly driven by abstinence from alcohol. With the emerging data on the benefits of liver transplantation, liver transplantation could be an important salvage option for a very highly select group of AH patients. More data are needed on the use of liver transplantation in AH as the basis for deriving protocols for selecting cases and for posttransplant management. Currently, many clinical trials are examining the efficacy and safety of new or repurposed compounds in severe AH. These drugs are targeted at various pathways in the pathogenesis of AH: the gut-liver axis, the inflammatory cascade, and liver injury. With increasing interest of researchers and clinicians, supported by funding from the National Institute on Alcohol Abuse and Alcoholism, the future seems promising for the development of effective and safe pharmacological interventions for severe AH. PMID:26870933

  10. Acute Hepatic Porphyria

    PubMed Central

    Bissell, D. Montgomery; Wang, Bruce

    2015-01-01

    The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631

  11. New treatment options for alcoholic hepatitis

    PubMed Central

    Shasthry, Saggere Muralikrishna; Sarin, Shiv Kumar

    2016-01-01

    The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using “Omics” platforms, newer options for patients with alcoholic hepatitis are expected soon. PMID:27099434

  12. Zafirlukast-induced acute hepatitis.

    PubMed

    Su, Chien-Wei; Wu, Jaw-Ching; Huang, Yi-Hsiang; Huang, Yi-Shin; Chang, Full-Young; Lee, Shou-Dong

    2002-11-01

    Zafirlukast, a competitive cysteinyl leukotriene receptor antagonist, is a new class of asthma medications. It has shown an adverse event profile similar to that of placebo. Herein, we present a 69-year-old female patient who suffered from general malaise, poor appetite, nausea and jaundice after 3 months of zafirlukast therapy for asthma. She had no past history of liver disease, nor history of alcoholism, herb medication, blood transfusion, acupuncture, tattoo or recent traveling history. Liver biochemistries revealed elevated serum alanine aminotransferase and aspartase aminotransferase levels up to 481 U/L and 212 U/L, respectively. Moreover, peak serum total bilirubin level was elevated to 34.8 mg/dL during admission. Serum viral hepatitis marker, antinuclear antibody, anti-mitochondrial antibody and anti-smooth muscle antibody were all negative. Her general condition and liver biochemistries improved gradually after zafirlukast was discontinued. Roussel Uclaf causality assessment for adverse drug reaction confirmed the diagnosis of drug-induced liver injury. This case reminds us that zafirlukast is a potentially hepato-toxic drug. If clinical manifestations of hepatitis develop, patients should be managed cautiously and closely monitored for liver biochemistries. If drug-induced hepatitis is suspected, medication should be discontinued immediately to prevent further liver injury. PMID:12583521

  13. Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

    PubMed Central

    Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

    2014-01-01

    A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327

  14. [Hematologic complications in acute alcoholism].

    PubMed

    Popa, G; Niculescu, M; Iordăcheanu, L; Hurjui, V

    1978-01-01

    The authors investigated the relations between cell anomalies (vacuolation, increasing sideroblastosis) caused by the uptake of alcohol and the dynamics of haematopoesis in the bone-marrow of 33 alcoholists who had been admitted in a comatose condition and who were neither affected with anaemia nor with chronic hepatitis. In all cases a maturation arrest of erythropoetic and granulopoetic cell elements which was not in accordance with the number of immature vacuolated cells could be observed. 12 test persons showed increased sideroblastic indices and a slightly diminished medullary reticulocytosis. The majority showed a very active thrombocytopoesis contrasting with the normal or even diminished number of thrombocytes in the peripheral blood. The authors come to the conclusion that alcohol will cause a general metabolic damage of haematopoesis and at the same time it will produce a direct toxic effect on the bone-marrow cells (proerythroblasts, promyelocytes) and the peripheral blood (thrombocytes). PMID:77822

  15. Chronic urticaria following acute hepatitis A

    PubMed Central

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

    2012-01-01

    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. PMID:22989421

  16. Hepatic glutathione content in patients with alcoholic and non alcoholic liver diseases

    SciTech Connect

    Altomare, E.; Vendemiale, G.; Albano, O.

    1988-01-01

    Reduced and oxidized hepatic glutathione was evaluated during alcoholic and non alcoholic liver injury. We studied 35 chronic alcoholics, 20 patients with non alcoholic liver diseases, 15 control subjects. Hepatic glutathione was measured in liver biopsies and correlated with histology and laboratory tests. Alcoholic and non alcoholic patients exhibited a significant decrease of hepatic glutathione compared to control subjects. Oxidized glutathione was significantly higher in the two groups of patients compared to controls. The decreased hepatic glutathione level in patients with alcoholic and non alcoholic liver diseases may represent a contributing factor of liver injury and may enhance the risk of toxicity in these patients.

  17. Acute Abdomen Caused by Brucellar Hepatic Abscess.

    PubMed

    Koca, Yavuz Savas; Barut, Ibrahim; Koca, Tugba; Kaya, Onur; Aktas, Recep Aykut

    2016-01-01

    Brucellosis, a zoonosis that is common worldwide, is endemic in many countries, primarily those of the Mediterranean region (including Turkey). 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 spp. infection. We present a case of hepatic abscess caused by Brucella melitensis, which resembled the clinical presentation of surgical acute abdomen. PMID:26526924

  18. Acute abdomen caused by brucellar hepatic abscess.

    PubMed

    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. PMID:17962133

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

    PubMed

    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. PMID:26691320

  20. Hepatitis B virus persistence after recovery from acute viral hepatitis.

    PubMed Central

    Michalak, T I; Pasquinelli, C; Guilhot, S; Chisari, F V

    1994-01-01

    Contrary to current opinion, the disappearance of hepatitis B surface antigen (HBsAg) from the serum, the development of anti-HBs antibodies, and normalization of liver function may not reflect complete virological recovery from acute hepatitis B virus (HBV) infection. By using the polymerase chain reaction (PCR), in the current study we demonstrate long-term persistence of HBV DNA in the serum and peripheral blood mononuclear cells (PBMC) of four patients for up to 70 mo after complete clinical, biochemical, and serological recovery from acute viral hepatitis. Serum HBV DNA reactivity co-sedimented with HBsAg in sucrose gradients, and it displayed the size and density characteristics of naked core particles and intact HBV virions, presumably contained within circulating immune complexes in these anti-HBs antibody-positive sera. HBV DNA was also present in PBMC in late convalescent samples from all four patients, and HBV RNA was detected in late convalescent phase PBMC in two of these patients. These results suggest that HBV DNA, and possibly HBV virions, can be present in the serum, and that the viral genome can persist in a transcriptionally active form in PBMC for > 5 yr after complete clinical and serological recovery from acute viral hepatitis. Images PMID:8282792

  1.  Alcoholic hepatitis: How far are we and where are we going?

    PubMed

    Prado, Verónica; Caballería, Joan; Vargas, Víctor; Bataller, Ramón; Altamirano, José

    2016-01-01

     The burden of alcoholic liver disease continues to be a major public health problem worldwide. The spectrum of disease ranges from fatty liver to cirrhosis and hepatocellular carcinoma. Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and the most severe form of alcoholic liver disease. Severe AH carries a poor short-term prognosis and its management is still challenging, with scarce advances in the last decades. Corticosteroids are still the first line of therapy in severe cases. Unfortunately, many patients do not respond and novel targeted therapies are urgently needed. Liver transplantation has shown extraordinary results in non-responders to corticosteroids however; its applicability is very low. This review summarizes the epidemiology, natural history, risk factors and pathogenesis of alcoholic liver disease with special focus on the latest advances in prognostic stratification and therapy of patients with alcoholic hepatitis. PMID:27236145

  2. Acute esophageal necrosis caused by alcohol abuse

    PubMed Central

    Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

    2005-01-01

    Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

  3. Combination therapy: New hope for alcoholic hepatitis?

    PubMed

    Gao, Bin; Shah, Vijay H

    2015-09-01

    Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease with high mortality. The pathogenesis of AH is not fully understood, but it is generally believed that inflammation is a key factor leading to liver failure in AH. Steroids, which have broad immunosuppressive effects, have been used for the treatment of AH over the last forty years. Steroids elicit modest improvement in short-term survival rate in patients with severe AH, but also cause severe side effects. Several specific inflammatory targets (e.g., IL-1, LPS, and gut microbiota) are currently under investigation for the treatment of AH with the goal to obviate or reduce steroid administration. In addition to inflammation, impaired liver regeneration is another major cause of liver failure in AH, which deteriorates further after steroid treatment because inflammation plays a key role in promoting liver repair. Interleukin-22 (IL-22) is a promising drug for the treatment of AH because of its hepatoprotective and anti-fibrotic functions and relatively few known side effects. In addition, IL-22 treatment also ameliorates bacterial infection and kidney injury, two major complications associated with severe AH. IL-22 is currently under investigation in preclinical and clinical studies and may hold great promise for AH by providing more beneficial effects and fewer side effects than current therapies. PMID:26193867

  4. An outbreak of refrigerant-induced acute hepatitis in Hong Kong.

    PubMed

    Kan, Y M; Lau, C F; Chan, W C; Chan, W S; Tung, Y M; Loo, C K

    2014-12-01

    We report a cluster of acute hepatitis in five air-conditioning maintenance workers following accidental exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123). They presented to us with complaints of feverishness, generalised malaise, and epigastric discomfort. Their blood biochemistry tests were compatible with acute hepatitis. Viral hepatitis serology, tests for autoimmune hepatitis, and analyses for drugs and alcohol consumption were all negative. No focal hepatic lesion was detected by ultrasound imaging. Percutaneous liver biopsy samples were taken from two of them. The patients were managed with supportive treatment. All had spontaneous, but slow, recovery. Their liver function tests returned to normal after 4 months and their outcomes were favourable. Physicians should be aware of this occupational disease entity. PMID:25488036

  5. Do Cinnamon Supplements Cause Acute Hepatitis?

    PubMed Central

    Brancheau, Daniel; Patel, Brijesh; Zughaib, Marcel

    2015-01-01

    Patient: Female, 73 Final Diagnosis: Drug induced acute hepatitis Symptoms: Abdominal pain • diarrhea • vomiting Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Unusual or unexpected effect of treatment Background: The use of herbal medications to treat various diseases is on the rise. Cinnamon has been reported to improve glycolated hemoglobin and serum glucose levels. When patients consider the benefit of such substances, they are often not aware of potential adverse effects and drug interactions. Cinnamon, via coumarin, can cause liver toxicity. Therefore, its concomitant use with hepatotoxic drugs should be avoided. Case Report: A 73-year-old woman was seen in the Emergency Department complaining of abdominal pain associated with vomiting and diarrhea after she started taking cinnamon supplements for about 1 week. The patient had been taking statin for coronary artery disease for many months. The laboratory workup and imaging studies confirmed the diagnosis of hepatitis. The detail workup did not reveal any specific cause. Cinnamon and statin were held. A few weeks after discharge, the statin was resumed without any further complications. This led to a diagnosis of cinnamon-statin combination-induced hepatitis. Conclusions: A combination of cinnamon supplement and statin can cause hepatitis, and it should be discouraged. PMID:25923145

  6. Natural history of alcoholic hepatitis. IV. Glycosaminoglycuronans and collagen in the hepatic connective tissue.

    PubMed

    Galambos, J T; Shapira, R

    1973-11-01

    The extractable and nonextractable collagen and glycosaminoglycuronans (GAG) were estimated and characterized in 32 dried, defatted human livers obtained at necropsy. 10 had normal livers. 22 of the 32 livers were from patients who drank in excess: 5 had fatty livers, 7 had alcholic hepatitis, and 10 had cirrhosis. Livers with alcoholic hepatitis or cirrhosis had significantly increased total and 1 N NaCl-extractable collagen. Only alcoholic hepatitis livers had significantly increased Tris-buffer-extractable GAG, but the amino acid composition of these GAG (proteoglycans) was no different from that of normal livers. The major fraction of these GAG had isoelectric pH (pI) alcoholic hepatitis or cirrhosis had significantly increased nonextractable GAG. The major GAG fraction of all livers was chondroitin-4 or -6-SO(4). Alcoholic hepatitis livers had a significant increase of hyaluronic acid and an unidentified hyaluronidase-resistant GAG. Fatty livers showed no differences from normal ones. The data indicates that alcoholic hepatitis is associated with a significantly increased fibroblast activity, but fatty livers of alcoholics are not. The changes in histologically "inactive" micronodular cirrhosis of alcoholic patients indicate continued activity of fibroblasts in the connective tissue of these cirrhotic livers. PMID:4270646

  7. Acute hepatic failure among hospitalized Thai children.

    PubMed

    Poovorawan, Yong; Chongsrisawat, Voranush; Shafi, Fakrudeen; Boudville, Irving; Liu, Yanfang; Hutagalung, Yanee; Bock, Hans L

    2013-01-01

    We conducted a hospital-based study from June 2002 to December 2006 of Thai children aged 1-15 years with acute hepatic failure (AHF) to determine the causes and outcomes. Eleven children were included in the study. Hepatitis B virus was the cause of AHF in one child, infection-associated hemophagocytic syndrome was the cause in 1 child, Wilson's disease was the cause in 1 child and dengue fever was suspected to be the cause in 2 children. In 6 children the cause of AHF was unknown. Jaundice was reported in 9 of 11 children. Ten of 11 children had mild to moderate encephalopathy on admission. Five of 11 children died due to AHF. No liver transplantations were performed among the children in this study. Further studies into the relationship between dengue infection and AHF are needed. PMID:23682437

  8. Lipid peroxidation and hepatic antioxidants in alcoholic liver disease.

    PubMed Central

    Situnayake, R D; Crump, B J; Thurnham, D I; Davies, J A; Gearty, J; Davis, M

    1990-01-01

    The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation. PMID:2253918

  9. [Action of analeptics in acute alcoholic intoxication].

    PubMed

    Bender, K I; Bobrova, L A

    1978-01-01

    Tests conducted on rabbits in a state of acute ethanol poisoning (2.5 g/kg per os) of a medium degree demonstrated that caffein (10 mg/kg) and bemegride (5 mg/kg) introduced one time intravenously at the height of alcoholic intoxication raise the activity of aerobic oxidative processes, but fail to eliminate metabolic acidosis and do not accelerate the excretion of ethanol. Unlike caffein, bemegride shows a tendency toward respiratory compensation of metabolic acidosis and lowers the activity of the alcohol-dehydrogenase. PMID:26595

  10. Acute interstitial nephritis with acetaminophen and alcohol intoxication.

    PubMed

    Fruchter, Lauren L; Alexopoulou, Iakovina; Lau, Keith K

    2011-01-01

    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. PMID:21496243

  11. Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis

    PubMed Central

    Rudler, Marika; Mouri, Sarah; Charlotte, Frederic; Cluzel, Philippe; Ngo, Yen; Munteanu, Mona; Lebray, Pascal; Ratziu, Vlad; Thabut, Dominique; Poynard, Thierry

    2015-01-01

    Background/Aims According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. Methods The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. Results A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification. Conclusion These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy. PMID:26252713

  12. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland

    PubMed Central

    Kokki, I.; Smith, D.; Simmonds, P.; Ramalingam, S.; Wellington, L.; Willocks, L.; Johannessen, I.; Harvala, H.

    2015-01-01

    Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID:26904201

  13. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland.

    PubMed

    Kokki, I; Smith, D; Simmonds, P; Ramalingam, S; Wellington, L; Willocks, L; Johannessen, I; Harvala, H

    2016-03-01

    Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID:26904201

  14. Decreased hepatic iron in response to alcohol may contribute to alcohol-induced suppression of hepcidin.

    PubMed

    Varghese, Joe; James, Jithu Varghese; Sagi, Sreerohini; Chakraborty, Subhosmito; Sukumaran, Abitha; Ramakrishna, Banumathi; Jacob, Molly

    2016-06-01

    Hepatic Fe overload has often been reported in patients with advanced alcoholic liver disease. However, it is not known clearly whether it is the effect of alcohol that is responsible for such overload. To address this lacuna, a time-course study was carried out in mice in order to determine the effect of alcohol on Fe homoeostasis. Male Swiss albino mice were pair-fed Lieber-DeCarli alcohol diet (20 % of total energy provided as alcohol) for 2, 4, 8 or 12 weeks. Expression levels of duodenal and hepatic Fe-related proteins were determined by quantitative PCR and Western blotting, as were Fe levels and parameters of oxidative stress in the liver. Alcohol induced cytochrome P4502E1 and oxidative stress in the liver. Hepatic Fe levels and ferritin protein expression dropped to significantly lower levels after 12 weeks of alcohol feeding, with no significant effects at earlier time points. This was associated, at 12 weeks, with significantly decreased liver hepcidin expression and serum hepcidin levels. Protein expressions of duodenal ferroportin (at 8 and 12 weeks) and divalent metal transporter 1 (at 8 weeks) were increased. Serum Fe levels rose progressively to significantly higher levels at 12 weeks. Histopathological examination of the liver showed mild steatosis, but no stainable Fe in mice fed alcohol for up to 12 weeks. In summary, alcohol ingestion by mice in this study affected several Fe-related parameters, but produced no hepatic Fe accumulation. On the contrary, alcohol-induced decreases in hepatic Fe levels were seen and may contribute to alcohol-induced suppression of hepcidin. PMID:27080262

  15. Alcoholic hepatitis: The pivotal role of Kupffer cells.

    PubMed

    Suraweera, Duminda B; Weeratunga, Ashley N; Hu, Robert W; Pandol, Stephen J; Hu, Richard

    2015-11-15

    Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis (AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides (LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called toll-like receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis. PMID:26600966

  16. Alcoholic hepatitis: The pivotal role of Kupffer cells

    PubMed Central

    Suraweera, Duminda B; Weeratunga, Ashley N; Hu, Robert W; Pandol, Stephen J; Hu, Richard

    2015-01-01

    Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis (AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides (LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called toll-like receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis. PMID:26600966

  17. Hepatitis C, Innate Immunity and Alcohol: Friends or Foes?

    PubMed Central

    Osna, Natalia A.; Ganesan, Murali; Kharbanda, Kusum K.

    2015-01-01

    Hepatitis C and alcohol are the most widespread causes of liver disease worldwide. Approximately 80% of patients with a history of hepatitis C and alcohol abuse develop chronic liver injury. Alcohol consumption in hepatitis C virus (HCV)-infected patients exacerbates liver disease leading to rapid progression of fibrosis, cirrhosis and even hepatocellular carcinoma. Hepatocytes are the main sites of HCV-infection and ethanol metabolism, both of which generate oxidative stress. Oxidative stress levels affect HCV replication and innate immunity, resulting in a greater susceptibility for HCV-infection and virus spread in the alcoholic patients. In this review paper, we analyze the effects of ethanol metabolism and other factors on HCV replication. In addition, we illustrate the mechanisms of how HCV hijacks innate immunity and how ethanol exposure regulates this process. We also clarify the effects of HCV and ethanol metabolism on interferon signaling—a crucial point for activation of anti-viral genes to protect cells from virus—and the role that HCV- and ethanol-induced impairments play in adaptive immunity which is necessary for recognition of virally-infected hepatocytes. In conclusion, ethanol exposure potentiates the suppressive effects of HCV on innate immunity, which activates viral spread in the liver and finally, leads to impairments in adaptive immunity. The dysregulation of immune response results in impaired elimination of HCV-infected cells, viral persistence, progressive liver damage and establishment of chronic infection that worsens the outcomes of chronic hepatitis C in alcoholic patients. PMID:25664450

  18. Severe alcoholic hepatitis: Glucocorticoid saves lives and transplantation is promising

    PubMed Central

    Braillon, Alain

    2011-01-01

    Glucocorticosteroids have been used as the only treatment for a long time which significantly reduced the mortality of the patients with severe alcoholic hepatitis. The efficacy of transplantation has been recently addressed in a pilot study. The result seems promising but needs larger multicenter trials. PMID:21633648

  19. Cinnamon extract protects against acute alcohol-induced liver steatosis in mice.

    PubMed

    Kanuri, Giridhar; Weber, Synia; Volynets, Valentina; Spruss, Astrid; Bischoff, Stephan C; Bergheim, Ina

    2009-03-01

    Acute and chronic consumption of alcohol can cause increased intestinal permeability and bacterial overgrowth, thereby increasing portal endotoxin levels. This barrier impairment subsequently leads to an activation of hepatic Kupffer cells and increased release of reactive oxygen species as well as of tumor necrosis factor-alpha (TNFalpha). Recent studies have suggested that cinnamon extract may have antiinflammatory effects. In the present study, the protective effects of an alcoholic extract of cinnamon bark was assessed in a mouse model of acute alcohol-induced steatosis and in RAW 264.7 macrophages, used here as a model of Kupffer cells. Acute alcohol ingestion caused a >20-fold increase in hepatic lipid accumulation. Pretreatment with cinnamon extract significantly reduced the hepatic lipid accumulation. This protective effect of cinnamon extract was associated with an inhibition of the induction of the myeloid differentiation primary response gene (MyD) 88, inducible nitric oxide (NO) synthase (iNOS), and plasminogen activator inhibitor 1 mRNA expression found in livers of alcohol-treated animals. In vitro prechallenge with cinnamon extract suppressed lipopolysaccharide (LPS)-induced MyD88, iNOS, and TNFalpha expression as well as NO formation almost completely. Furthermore, LPS treatment of RAW 264.7 macrophages further resulted in degradation of inhibitor kappaB; this effect was almost completely blocked by cinnamon extract. Taken together, our data show that an alcohol extract of cinnamon bark may protect the liver from acute alcohol-induced steatosis through mechanisms involving the inhibition of MyD88 expression. PMID:19126670

  20. Failure of carnitine in improving hepatic nitrogen content in alcoholic and non‐alcoholic malnourished rats

    PubMed Central

    Rodrigues, Luciana P; Portari, Guilherme Vannucchi; Padovan, Gilberto João; Jordão, Alceu Afonso; Suen, Vivian M M; Sergio Marchini, Julio

    2010-01-01

    AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein‐calorie restriction with free access to water (malnutrition group) and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group) were studied. After the undernourishment period (4 weeks with or without alcohol), both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups) and the other re‐fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage) (carnitine groups). No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii) Liver nitrogen content was highest in the carnitine recovery non‐alcoholic group (from 1.7 to 3.3 g/100 g, P<0.05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (∼10 g/100 g, P>.05) was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery. PMID:21049216

  1. Development of a Measure of Hepatitis C-alcohol Knowledge

    PubMed Central

    Proeschold-Bell, Rae Jean; Yao, Jia; Gorthala, Sisira; Muir, Andrew

    2015-01-01

    Alcohol use by persons with hepatitis C (HCV) increases the risk of cirrhosis and hepatocellular carcinoma, yet no measures on knowledge of the effects of alcohol use on HCV have been published. We developed 7 items assessing knowledge of the relationship between HCV and alcohol use. We enrolled 53 patients with HCV and risky alcohol use in an HCV-alcohol treatment study. All 53 participants completed a baseline interview, with 35 and 45 participants completing additional interviews at three and six months, respectively. We used generalized estimating equations (GEE) regression to account for non-independence of subjects and attrition. We assessed changes in HCV-alcohol knowledge at three and six months compared to baseline. Knowledge significantly increased at three months, compared to baseline (β=0.392, p=0.005), and had a trend toward significance at six months, compared to baseline (β=0.232, p=0.074). We also tested for between-subject differences in HCV-alcohol knowledge by demographic variables. HCV-alcohol knowledge did not significantly vary by gender, age, baseline HIV status, or baseline depression. Participants with higher educational attainment (β=0.052, p=0.057) had a trend toward significantly higher HCV-alcohol knowledge scores, and White participants had higher HCV-alcohol knowledge scores (β=0.349, p=0.002) than participants of all other races combined. In a second GEE regression model, we examined the relationship between change in HCV-alcohol knowledge and change in alcohol use severity scores over time. Increases in one’s HCV-alcohol knowledge score were significantly related to greater reductions in alcohol use severity scores (β=−0.052, p=0.027). Thus, the seven-item HCV-alcohol Knowledge Scale successfully identified changes in HCV-alcohol knowledge after exposure to HCV-alcohol education. In addition, improvements in HCV-alcohol knowledge, as assessed by the scale, predicted decreases in alcohol use over time. These findings support the use of the HCV-alcohol Knowledge Scale as both a research and clinical tool.

  2. Aging and alcohol interact to alter hepatic DNA hydroxymethylation

    PubMed Central

    Tammen, Stephanie A.; Dolnikowski, Gregory G.; Ausman, Lynne M.; Liu, Zhenhua; Sauer, Julia; SimonettaFriso; Choi, Sang-Woon

    2014-01-01

    Background Aging and chronic alcohol consumption are both modifiers of DNA methylation but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression. Methods Old (18 months) and young (4 months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloricLieber-DeCarli control diet for 5 weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new LC/MS-MS method. Hepatic mRNA expression of the Tet enzymes and Cyp2e1 were measured via qRTPCR. Results In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22%±0.01% vs 0.29±0.06%, p = 0.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24±0.02% vs 0.29±0.06%, p = 0.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction = 0.009). Expression of Tet2 and Tet3 enzymes was decreased in the old mice relative to the young (p < 0.005). Conclusions The observation that alcohol alters DNA hydroxymethylation indicates a new epigenetic effect of alcohol. This is the first study demonstrating the interactive effects of chronic alcohol consumption and aging on DNA hydroxymethylation. PMID:25070523

  3. Vascular thrombosis in acute hepatic allograft rejection: scintigraphic appearance

    SciTech Connect

    Williams, H.C.; Pope, C.F.; Siskind, B.N.; Lange, R.C.; Flye, M.W.

    1985-05-01

    Hepatobiliary imaging with /sup 99m/Tc diisopropyl iminodiacetic acid was employed serially in a patient with an hepatic allograft, in order to follow the function of the transplant. Initially improving liver uptake and biliary excretion was observed; however, 12 days postoperative with clinical deterioration the scintigrams revealed an absence of uptake (phantom liver), due to thrombosis of the hepatic artery related to acute rejection. Hepatobiliary imaging can be helpful in the study of hepatic allografts.

  4. Cytochrome P4502E1, oxidative stress, JNK, and autophagy in acute alcohol-induced fatty liver.

    PubMed

    Yang, Lili; Wu, Defeng; Wang, Xiaodong; Cederbaum, Arthur I

    2012-09-01

    Binge alcohol drinking induces hepatic steatosis. Recent studies showed that chronic ethanol-induced fatty liver was, at least in part, CYP2E1 dependent. The mechanism of acute alcohol-induced steatosis and whether CYP2E1 plays any role are still unclear. Increasing oxidative stress by alcohol can activate the JNK MAP kinase signaling pathway, suggesting that JNK might be a target for prevention of alcohol-induced steatosis. We used CYP2E1 knockout (KO) mice, a JNK inhibitor, and JNK1 or JNK2 knockout mice to test the role of CYP2E1, JNK, and the individual role of JNK1 and JNK2 in acute alcohol-induced steatosis. In wild-type (WT) mice, acute alcohol activates CYP2E1 and increases oxidative stress, which reciprocally increases activation of the JNK signaling pathway. Acute alcohol-induced fatty liver and oxidative stress were blunted in CYP2E1 KO mice and by the JNK inhibitor in WT mice. The antioxidant N-acetylcysteine decreased the acute alcohol-induced oxidative stress, the activation of JNK, and the steatosis but not the activation of CYP2E1. Acute alcohol decreased autophagy and increased expression of SREBP, effects blocked by the JNK inhibitor. Acute alcohol-induced fatty liver was the same in JNK1 and JNK2 KO mice as in WT mice; thus either JNK1 or JNK2 per se is sufficient for induction of steatosis by acute alcohol. The results show that acute alcohol elevation of CYP2E1, oxidative stress, and activation of JNK interact to lower autophagy and increase lipogenic SREBP resulting in fatty liver. PMID:22749809

  5. Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol

    PubMed Central

    Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

    2015-01-01

    AIM: To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. METHODS: Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. RESULTS: In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. CONCLUSION: It is feasible to establish an animal model of hepatic cirrhosis and portal hypertension by hepatic arterial perfusion with 80% alcohol, however, the safety of this model depends on a suitable perfusion dose. PMID:26327762

  6. Estimating Acute Viral Hepatitis Infections From Nationally Reported Cases

    PubMed Central

    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

  7. Alcoholic liver disease and hepatitis C virus infection.

    PubMed

    Novo-Veleiro, Ignacio; Alvela-Suárez, Lucía; Chamorro, Antonio-Javier; González-Sarmiento, Rogelio; Laso, Francisco-Javier; Marcos, Miguel

    2016-01-28

    Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection. PMID:26819510

  8. Alcoholic liver disease and hepatitis C virus infection

    PubMed Central

    Novo-Veleiro, Ignacio; Alvela-Suárez, Lucía; Chamorro, Antonio-Javier; González-Sarmiento, Rogelio; Laso, Francisco-Javier; Marcos, Miguel

    2016-01-01

    Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection. PMID:26819510

  9. Acute hepatitis B of genotype H resulting in persistent infection

    PubMed Central

    Yamada, Norie; Shigefuku, Ryuta; Sugiyama, Ryuichi; Kobayashi, Minoru; Ikeda, Hiroki; Takahashi, Hideaki; Okuse, Chiaki; Suzuki, Michihiro; Itoh, Fumio; Yotsuyanagi, Hiroshi; Yasuda, Kiyomi; Moriya, Kyoji; Koike, Kazuhiko; Wakita, Takaji; Kato, Takanobu

    2014-01-01

    A 47-year-old man presented with general fatigue and dark urine. The laboratory data showed increased levels of hepatic transaminases. The patient was positive for hepatitis B virus (HBV) markers and negative for anti-human immunodeficiency virus. The HBV-DNA titer was set to 7.7 log copies/mL. The patient was diagnosed with acute hepatitis B. The HBV infection route was obscure. The serum levels of hepatic transaminases decreased to normal ranges without any treatment, but the HBV-DNA status was maintained for at least 26 mo, indicating the presence of persistent infection. We isolated HBV from the acute-phase serum and determined the genome sequence. A phylogenetic analysis revealed that the isolated HBV was genotype H. In this patient, the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077 and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic infection. This case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis; further cases of HBV genotype H infection must be identified and characterized. Thus, the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients. PMID:24659896

  10. Acute renal failure associated with acute non-fulminant hepatitis B.

    PubMed

    Kishi, Tomoya; Ikeda, Yuji; Takashima, Tsuyoshi; Rikitake, Shuichi; Miyazono, Motoaki; Aoki, Shigehisa; Sakemi, Takanobu; Mizuta, Toshihiko; Fujimoto, Kazuma

    2013-02-27

    A 38-year-old female presenting with a high fever of 39 °C developed severe liver dysfunction and acute renal failure (ARF). In tests for a hepatitis associated virus, an Immunoglobulin M-anti-hepatitis B virus core antibody was the only positive finding. Moreover, the progression of ARF coincided with the pole period of liver damage and all the other assumed causes for the ARF were unlikely. Therefore, this case was diagnosed as ARF caused by acute hepatitis B. ARF associated with non-fulminant hepatitis has been infrequently reported, usually in association with acute hepatitis A. This case is considered to be an extremely rare and interesting case. PMID:23646233

  11. Occurrence of hepatitis and hepatitis B surface antigen in adult patients with acute leukemia.

    PubMed Central

    Cowan, D. H.; Kouroupis, G. M.; Leers, W. D.

    1975-01-01

    Fifty-eight adult patients with acute leukemia were screened at the onset of the disease for hepatitis B antigen (HBSAg) in the serum, and during the course of the disease for the development of hepatitis B. One patient had a positive test for HBSAg by the radioimmunoassay technique only at the time leukemia was diagnosed; this patient had received transfusions some years before. In six patients icteric hepatitis B developed; five recovered completely and one died of leukemia during the course of hepatitis. All patients in whom hepatitis developed had received transfusions as a part of supportive therapy for leukemia. The hepatitis risk for patients who received transfusions of blood found to be negative for HBSAg by counterimmunoelectrophoresis was 0.26 percent per unit of blood administered. PMID:1054615

  12. Role of osteopontin in hepatic neutrophil infiltration during alcoholic steatohepatitis

    SciTech Connect

    Apte, Udayan M.; Banerjee, Atrayee; McRee, Rachel; Wellberg, Elizabeth; Ramaiah, Shashi K. . E-mail: sramaiah@cvm.tamu.edu

    2005-08-22

    Alcoholic liver disease (ALD) is a major complication of heavy alcohol (EtOH) drinking and is characterized by three progressive stages of pathology: steatosis, steatohepatitis, and fibrosis/cirrhosis. Alcoholic steatosis (AS) is the initial stage of ALD and consists of fat accumulation in the liver accompanied by minimal liver injury. AS is known to render the hepatocytes increasingly sensitive to toxicants such as bacterial endotoxin (LPS). Alcoholic steatohepatitis (ASH), the second and rate-limiting step in the progression of ALD, is characterized by hepatic fat accumulation, neutrophil infiltration, and neutrophil-mediated parenchymal injury. However, the pathogenesis of ASH is poorly defined. It has been theorized that the pathogenesis of ASH involves interaction of increased circulating levels of LPS with hepatocytes being rendered highly sensitive to LPS due to heavy EtOH consumption. We hypothesize that osteopontin (OPN), a matricellular protein (MCP), plays an important role in the hepatic neutrophil recruitment due to its enhanced expression during the early phase of ALD (AS and ASH). To study the role of OPN in the pathogenesis of ASH, we induced AS in male Sprague-Dawley rats by feeding EtOH-containing Lieber-DeCarli liquid diet for 6 weeks. AS rats experienced extensive fat accumulation and minimal liver injury. Moderate induction in OPN was observed in AS group. ASH was induced by feeding male Sprague-Dawley rats EtOH-containing Lieber-DeCarli liquid diet for 6 weeks followed by LPS injection. The ASH rats had substantial neutrophil infiltration, coagulative oncotic necrosis, and developed higher liver injury. Significant increases in the hepatic and circulating levels of OPN was observed in the ASH rats. Higher levels of the active, thrombin-cleaved form of OPN in the liver in ASH group correlated remarkably with hepatic neutrophil infiltration. Finally, correlative studies between OPN and hepatic neutrophil infiltration was corroborated in a simple rat peritoneal model where enhanced peritoneal fluid neutrophil infiltration was noted in rats injected OPN intraperitoneally. Taken together these data indicate that OPN expression induced during ASH may play a significant role in the pathogenesis of ASH by stimulating neutrophil transmigration.

  13. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

    PubMed Central

    Groebner, Jennifer L.; Tuma, Pamela L.

    2015-01-01

    The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease. PMID:26393662

  14. The acute hepatic porphyrias: current status and future challenges.

    PubMed

    Siegesmund, Marko; van Tuyll van Serooskerken, Anne-Moniek; Poblete-Gutiérrez, Pamela; Frank, Jorge

    2010-10-01

    The porphyrias are predominantly inherited metabolic disorders, which result from a specific deficiency of one of the eight enzymes along the pathway of haem biosynthesis. Historically, they have been classified into hepatic and erythropoietic forms, based on the primary site of expression of the prevailing dysfunctional enzyme. From a clinical point of view, however, it is more convenient to subdivide them into acute and non-acute porphyrias, thereby primarily considering the potential occurrence of life-threatening acute neurovisceral attacks. Unrecognised or untreated, such an acute porphyric attack is associated with a significant mortality of up to 10%. The acute hepatic porphyrias comprise acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase deficiency porphyria. Making a precise diagnosis may be difficult because the different types of porphyrias may show overlapping clinical and biochemical characteristics. To date, the therapeutic possibilities are limited and mainly symptomatic. In this overview we report on what is currently known about pathogenesis, clinic, diagnostics, and therapy of the acute hepatic porphyrias. We further point out actual and future challenges in the management of these diseases. PMID:20955962

  15. Serum type III procollagen peptide and laminin (Lam-P1) detect alcoholic hepatitis in chronic alcohol abusers.

    PubMed

    Annoni, G; Colombo, M; Cantaluppi, M C; Khlat, B; Lampertico, P; Rojkind, M

    1989-05-01

    The diagnosis of alcoholic hepatitis is difficult to establish by conventional clinical and laboratory methods, and a firm diagnosis relies on liver histology. Since there are severe limitations in following patients with repeated liver biopsies, noninvasive procedures are needed to assess the presence of alcoholic hepatitis in chronic alcohol abusers. It has been suggested that serum Type III procollagen peptide levels correlates with the degree of inflammation in chronic liver disease. Since inflammation is a major histological finding in alcoholic hepatitis, we therefore studied the usefulness of measuring serum Type III procollagen peptide and laminin values in 45 consecutive chronic alcohol abusers, with or without cirrhosis, in detecting those with alcoholic hepatitis. The results showed that both Type III procollagen peptide and laminin values were elevated in all of the patients with established liver damage. However, the values were highest in those with liver cirrhosis plus alcoholic hepatitis (Type III procollagen peptide 50.4 +/- 36.4 ng per ml vs. 8.1 +/- 2.6 in controls, p less than 0.01; laminin 4.50 +/- 1.49 units per liter vs. 1.24 +/- 0.26 units per liter in controls, p less than 0.01), followed by subjects with alcoholic hepatitis alone (Type III procollagen peptide 23.5 +/- 17.6 ng per ml, p less than 0.01; laminin 2.60 +/- 1.09 units per liter, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2707736

  16. Pharmacodynamic Effects of Intravenous Alcohol on Hepatic and Gonadal Hormones: Influence of Age and Sex

    PubMed Central

    Vatsalya, Vatsalya; Issa, Julnar E.; Hommer, Daniel W.; Ramchandani, Vijay A.

    2011-01-01

    Background Growth Hormone (GH) - Insulin-like Growth Factor 1 (IGF-1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GH–IGF-1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Methods Forty-eight healthy volunteers (24 males and 24 females each in the 21–25 and 55–65 year age groups, underwent a two-session single-blinded study. Subjects received, in randomized counter-balanced order, alcohol infusions, individually computed based on a physiologically-based pharmacokinetic (PBPK) model, to maintain a steady-state (“clamped”) exposure of 50 mg% or saline for 3 hrs in separate sessions. Blood samples collected at baseline and post-infusion in each session were assayed for levels of GH, IGF-1, free testosterone and estradiol. Results Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment × baseline interaction (p<0.001), indicating that alcohol-induced suppression of testosterone occurred predominantly in males, On the other hand, change in estradiol showed a significant treatment × sex interaction (p=0.028), indicating that alcohol-induced increases in estradiol occurred predominantly in females. There was a trend for alcohol-induced decreases in IGF-1 levels. Change in GH showed a significant main effect of baseline (p<0.001) and a trend for treatment by baseline interaction, suggesting an alcohol-induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p=0.046) indicating that males had greater changes in GH across treatment compared to females. Conclusion Alcohol induced a complex pattern of hormonal responses that varied between younger and older males and females. Some of the observed sex-based differences may help improve our understanding of the greater susceptibility to alcohol-related hepatic damage seen in females. PMID:21797891

  17. The concanavalin A model of acute hepatitis in mice.

    PubMed

    Heymann, F; Hamesch, K; Weiskirchen, R; Tacke, F

    2015-04-01

    The intravenous injection of the plant lectin concanavalin A (ConA) is a widely used model for acute immune-mediated hepatitis in mice. In contrast to several other models for acute hepatic damage, ConA-induced injury is primarily driven by the activation and recruitment of T cells to the liver. Hence, the ConA model has unique features with respect to its pathogenesis and important similarities to immune-mediated hepatitis in humans, such as autoimmune hepatitis, acute viral hepatitis or distinct entities of drug toxicity leading to immune activation. However, the ConA model has considerable variability, depending on the preparation of the compound, genetic background of the mice, sex, age and microbial environment of the animal facility barrier. This standard operating procedure (SOP) comprises a detailed protocol for the ConA application, including preparation of ConA working solution, handling of the animals, choice of the appropriate conditions and endpoints, as well as efficient dose-finding. PMID:25835734

  18. [Can the L/A ratio identify acute alcoholic pancreatitis?].

    PubMed

    Deltenre, P; Ghilain, J M; Maisin, J M; Schapira, M; Henrion, J; Heller, F R

    1995-01-01

    Early distinction between acute alcoholic pancreatitis is important, because of possible emergency endoscopic sphincterotomy in case of biliary pancreatitis. The aim of this study was to evaluate the value of L/A ratio in the diagnosis of acute alcoholic pancreatitis. From 1990 to end 1993, 133 patients with acute pancreatitis were reviewed. Inclusion criteria were: 1) abdominal pain, 2) pathological serum amylase or serum lipase on admission or within 24 hours after beginning or abdominal pain, 3) acute pancreatitis at the echography or CT scan within 48 hours after admission. 60 patients met the inclusion criteria (31 alcoholic pancreatitis, 19 biliary pancreatitis and 10 pancreatitis of other causes). L/A ratio was studied in terms of delay from beginning of abdominal pain. There was no statistical difference between alcoholic and biliary pancreatitis at any time of the study, with the exception of admission. AST, ALT and alkaline phosphatase were higher in biliary pancreatitis than in alcoholic pancreatitis. AST and ALT were the best biochemical tests to diagnose biliary pancreatitis. Blamey's criteria can also contribute to diagnose biliary pancreatitis. These biochemical tests are the most helpful if they are collected very soon in the evolution of acute pancreatitis. It is concluded that L/A ratio is not helpful in the diagnosis of alcoholic acute pancreatitis. PMID:7571983

  19. Trypsin activity. A new marker of acute alcoholic pancreatitis.

    PubMed

    Le Moine, O; Devaster, J M; Devière, J; Thiry, P; Cremer, M; Ooms, H A

    1994-12-01

    A normal serum amylase level is found in up to 32% of patients with acute alcoholic pancreatitis. This underlines the need for more sensitive diagnostic tests in this frequent cause of pancreatitis. Animal and human studies have shown that chronic alcohol consumption leads to important modifications in trypsinogen metabolism. The present work has prospectively analyzed admission serum trypsin activity with a new biochemical test and usual markers such as amylase, lipase, and immunoreactive trypsin in 32 attacks of acute pancreatitis. Seventeen were due to alcohol and 15 to other causes, including 11 with gallstone pancreatitis. High trypsin activity (median: 235 units/liter; range: 165-853) was found in all patients with acute alcoholic pancreatitis even when the amylase level was normal on admission (3/17: 18%). Trypsin activity did not differ between nonalcoholic pancreatitis (N = 15): 84 units/liter (42-98), alcoholic controls (N = 15): 77 units/liter (40-122), and healthy controls (N = 62): 81 units/liter (15-143). The difference was not related to the severity of disease or circulating alpha 2-macroglobulin, alpha 1-protease inhibitor, or immunoreactive trypsinogen levels. Lipase/amylase ratio was less discriminant than trypsin activity between alcoholic and nonalcoholic diseases. We conclude that serum trypsin activity seems specific to acute alcoholic pancreatitis and should be included in new prospective studies assessing biochemical testing of alcohol-related pancreatic diseases. PMID:7527752

  20. Protective effect of bicyclol on acute alcohol-induced liver injury in mice.

    PubMed

    Zhao, Jing; Chen, Hui; Li, Yan

    2008-05-31

    Oxidative stress, cytokine over expression and Kupffer cell activation are well-documented pathological factors in the development of alcoholic liver disease. Bicyclol is a novel synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory property. The present study was to investigate the effect of bicyclol on acute alcohol-induced liver injury and related mechanisms in mice. Bicyclol (200, 300 mg/kg) was given to mice by gavage for three times. Alcohol (6 g/kg) was administered orally 1 h after the last dose of bicyclol. All animals were sacrificed at different time points after alcohol administration. Liver injury was evaluated by biochemical and histopathological examination. Lipid peroxidation and the activity of antioxidants were measured by spectrophotometric method. Expression of cytokines and CD14 were determined by enzyme-linked immunosorbent assay, reverse transcriptional-polymerase chain reaction and immunohistochemical staining. As a result, bicyclol pretreatment significantly protected against acute alcohol-induced liver injury as evidenced by the decrease of elevated serum alanine aminotransferase and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated the formation of thiobarbituric acid-reactive substance and restored impaired antioxidants, including glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Over-expression of cytokines, such as tumor necrosis factor alpha and interleukin 1beta, elevated plasma endotoxin level, and up-regulation of CD14 were also suppressed by bicyclol in alcohol-intoxicated mice. The protective effect of bicyclol on alcohol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the cytokine expression at both protein and gene level, and inhibit the activation of Kupffer cells by decreasing plasma endotoxin level and CD14 expression. PMID:18371952

  1. Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets.

    PubMed

    Kauma, H; Koskela, R; Mäkisalo, H; Autio-Harmainen, H; Lehtola, J; Höckerstedt, K

    2004-11-01

    In this report we describe a young, previously healthy woman who developed severe acute hepatitis after consumption of chaparral tablets, a commonly used herbal product. In this case, the elimination-rechallenge event and the exclusion of other possible aetiologic factors strongly supported true causality between the herbal product and the liver damage. Primary liver biopsy showed severe toxic hepatitis consistent with previous reports of chaparral-induced liver damage. Later, 6 months after the liver function tests had normalized, permanent hepatic fibrosis could still be seen. PMID:15545179

  2. Alcohol induced hepatic degeneration in a hepatitis C virus core protein transgenic mouse model.

    PubMed

    Noh, Dong-Hyung; Lee, Eun-Joo; Kim, Ah-Young; Lee, Eun-Mi; Min, Chang-Woo; Kang, Kyung-Ku; Lee, Myeong-Mi; Kim, Sang-Hyeob; Sung, Soo-Eun; Hwang, Meeyul; Yu, Dae-Yeul; Jeong, Kyu-Shik

    2014-01-01

    Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection. PMID:24608925

  3. Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus.

    PubMed

    Kao, J H; Chen, P J; Lai, M Y; Chen, D S

    2001-10-01

    There are 7 genotypes of hepatitis B virus (HBV). Whether superinfection of HBV carriers with different HBV genotypes occurs remains unknown. We therefore determined the HBV genotype and association between superinfection and acute exacerbation of disease in a cohort of 244 patients with chronic HBV infection who had elevated serum aminotransferase levels for at least 1 year. Within this group, 103 patients experienced acute exacerbation with an annual incidence of 13%, and 20 of the 103 patients had IgM antibody to hepatitis B core antigen (IgM anti-HBc). These 20 patients had a higher prevalence of genotype C infection (65%) than the remaining 83 anti-core IgM-negative patients (40%) who also had acute exacerbations (P <.05). Detailed analysis of HBV genotypes and sequences of the variable pre-S gene were determined in serial samples from 20 patients with IgM anti-HBc-positive acute exacerbations (group A), 20 patients with IgM anti-HBc-negative acute exacerbations (group B), and 20 patients without exacerbations (group C). Two (10%) of the group A patients had virologic evidence of HBV superinfection during acute exacerbation, one superinfected with heterotypic virus and the other with homotypic virus. The newly introduced virus disappeared after the exacerbation and the original virus resumed thereafter. The calculated prevalence of HBV superinfection in the hepatitis B carriers and those with acute exacerbations was 0.8% (2 of 244) and 1.9% (2 of 103), respectively. In conclusion, superinfection of HBV on hepatitis B carriers indeed occurs and may cause acute exacerbations, albeit at a low frequency even in hyperendemic areas of HBV infection. PMID:11584381

  4. The Protective Effects of Buzui on Acute Alcoholism in Mice

    PubMed Central

    Wen, Da-Chao; Gao, Shu-di; Hu, Xiao-yu; Yi, Cheng

    2016-01-01

    This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism. PMID:26884793

  5. The Protective Effects of Buzui on Acute Alcoholism in Mice.

    PubMed

    Chen, Chen; Wen, Da-Chao; Gao, Shu-di; Hu, Xiao-Yu; Yi, Cheng

    2016-01-01

    This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism. PMID:26884793

  6. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection.

    PubMed

    Leggio, L; Ferrulli, A; Zambon, A; Caputo, F; Kenna, G A; Swift, R M; Addolorato, G

    2012-04-01

    Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABA(B) receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some Liver Function Tests (LFTs) (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients. PMID:22244707

  7. Extent of the acute phase response in fulminant hepatic failure.

    PubMed Central

    Izumi, S; Hughes, R D; Langley, P G; Pernambuco, J R; Williams, R

    1994-01-01

    The extent of the acute phase response and the relation between acute phase proteins and cytokines in plasma was investigated in 50 patients with fulminant hepatic failure. On admission, C reactive protein was significantly higher in fulminant hepatic failure (median: 12.4 micrograms/ml, range:0.2-112 micrograms/ml) than in 20 controls (median: 0.8 microgram/ml, range: 0.3-2.9 micrograms/ml, p < 0.001). Serial measurements showed that plasma C reactive protein increased daily after admission until day 5, the end of the study period. alpha 1-Antitrypsin (AAT) (median: 69.1%, range: 27.5-124%) and fibrinogen (median: 1.10 g/l, range: 0-2.82 g/l) were significantly lower in fulminant hepatic failure on admission than in controls (AAT: median: 126%, range: 75.4-149%; fibrinogen: median 2.48 g/l, range: 1.82-3.39 g/l, p < 0.001) and did not change subsequently. Both AAT and fibrinogen were maintained at significantly higher concentrations in survivors than in those who did not. Bacterial infection occurred in 23 patients during the course of fulminant hepatic failure, but did not influence the concentrations of these three proteins. Interleukin 6 was significantly higher in fulminant hepatic failure (median: 21.2 pg/ml, range: 0-871 pg/ml) than in controls (median: 2.4 pg/ml, range: 1.5-8.2 pg/ml, p < 0.001). There was a significant correlation between interleukin 6 and the C reactive protein concentrations in patients with viral hepatitis on admission and in all patients 48 hours later, consistent with other evidence that interleukin 6 stimulates synthesis of this acute phase protein. PMID:8063228

  8. Blood Alcohol Content, Injury Severity and Acute Respiratory Distress Syndrome

    PubMed Central

    Afshar, Majid; Smith, Gordon S.; Terrin, Michael L.; Barrett, Matthew; Lissauer, Matthew E.; Mansoor, Sahar; Jeudy, Jean; Netzer, Giora

    2014-01-01

    Background Elevated blood alcohol content is a risk factor for injury. Associations of blood alcohol content with acute respiratory distress syndrome have not been conclusively established. We evaluated the association of a BAC >0 mg/dL with the intermediate outcomes, Injury Severity Score and Glasgow Coma Score, and their association with acute respiratory distress syndrome development. Methods Observational retrospective cohort study of 26,305 primary trauma admissions to a statewide referral trauma center from July 11, 2003 to October 31, 2011. Logistic regression was performed to assess the relationship between Admission blood alcohol content, Injury Severity Score, Glasgow Coma Score, and acute respiratory distress syndrome development within five days of admission. Results The case-rate for acute respiratory distress syndrome was 5.5% (1447). Blood alcohol content >0 mg/dL was associated with acute respiratory distress syndrome development in adjusted analysis (Odds Ratio 1.50; 95% Confidence Interval 1.33–1.71, p<0.001). High Injury Severity Score (≥16) had a stronger association with acute respiratory distress syndrome development (Odds Ratio 17.99; 95% Confidence Interval 15.51–20.86); as did low Glasgow Coma Score (≤8) (Odds Ratio 8.77; 95% Confidence Interval 7.64–10.07, p<0.001). Patients with low Glasgow Coma Score and high Injury Severity Score had the most frequent acute respiratory distress syndrome (33.6%) and the highest case fatality rate without acute respiratory distress syndrome (24.7%). Conclusions Elevated blood alcohol content is associated with acute respiratory distress syndrome development. In the analysis of alcohol exposure, Injury Severity Score and Glasgow Coma Score occur after alcohol ingestion, making them intermediate outcomes. Injury Severity Score and Glasgow Coma Score were strong predictors of acute respiratory distress syndrome and may be useful to identify at-risk patients. Elevated blood alcohol content may increase the frequency of the acute respiratory distress syndrome through influence on injury severity or independent molecular mechanisms which can be discriminated only in experimental models PMID:24854314

  9. [Acute effects of alcohol and chronic alcoholism as causes of violent crime].

    PubMed

    Pillmann, F; Ullrich, S; Draba, S; Sannemüller, U; Marneros, A

    2000-09-01

    To study the influence of alcohol and psychosocial variables on delinquent behavior, we coded data from the psychiatric evaluation of 254 defendants using a standardized score sheet, analyzing correlations between acute intoxication at the time of the crime (ICD 10:F10.0), diagnosis of alcohol dependency according to ICD 10 (F10.2), psycho-biographical variables, criminal history, and parameters relating to the index offence. We found that 64.6% of all defendants studied were intoxicated when committing the crime and 25.6% suffered from alcohol dependency. Alcohol intoxication correlated to occurrence of violent crime, cruelty in committing the index offence, and earlier convictions. Logistic regression, with demographic and psychosocial variables entered as covariables, revealed acute alcohol intoxication but not alcohol dependency as a predictor of violent crime (odds ratio 2.3, P = 0.02). Alcohol intoxication and dependency were also independent predictors of earlier convictions (intoxication, odds ratio 4.4, P = 0.0001; dependency, odds ratio 3.6, P = 0.003). Our findings support the hypothesis that acute alcohol intoxication, not dependency, influences violent crime in a direct manner. However, alcohol dependency predicts criminal recidivism. PMID:11042866

  10. Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption

    PubMed Central

    Clugston, Robin D.; Jiang, Hongfeng; Lee, Man Xia; Berk, Paul D.; Goldberg, Ira J.; Huang, Li-Shin; Blaner, William S.

    2013-01-01

    Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body’s retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption. A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minorRE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease. PMID:23583843

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

    PubMed Central

    Tholen, Aletta T. R.; Schinkel, Janke; Molenkamp, Richard; Ang, C. Wim

    2016-01-01

    Background 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. Objectives 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. Study design 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). Results 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. Conclusions 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. PMID:26840767

  12. Granulocytapheresis for the treatment of severe alcoholic hepatitis: a case series and literature review.

    PubMed

    Kamimura, Kenya; Imai, Michitaka; Sakamaki, Akira; Mori, Shigeki; Kobayashi, Masaaki; Mizuno, Ken-Ichi; Takeuchi, Manabu; Suda, Takeshi; Nomoto, Minoru; Aoyagi, Yutaka

    2014-02-01

    Severe alcoholic hepatitis has a high mortality rate due to limited therapeutic methods. Although corticosteroids have been used to control the inflammatory response, the outcomes vary and no standardized therapy has been established. Novel therapeutic approaches, such as anti-TNF-α, pentoxifilline, and others have been tested clinically on the basis of their cytokinemic pathophysiology with limited success. However, treatment of leukocytosis that causes cytokinemia and hepatic inflammation in patients via granulocytapheresis and leukocytapheresis showed promising results in a number of reports. Here, we report two cases of severe alcoholic hepatitis treated with granulocytapheresis. The liver function and inflammation recovered after the therapy. A review of 35 cases treated with granulocytapheresis and leukocytapheresis demonstrated their efficacy in treating alcoholic hepatitis by controlling leukocytosis as well as cytokines such as IL-8. Multidisciplinary treatment for severe alcoholic hepatitis should be considered case by case on the basis of the complexity and severity of the condition. PMID:24052196

  13. Alcohol Directly Stimulates Epigenetic Modifications in Hepatic Stellate Cells

    PubMed Central

    Page, Agata; Paoli, Pier P.; Hill, Stephen J.; Howarth, Rachel; Wu, Raymond; Kweon, Soo-Mi; French, Jeremy; White, Steve; Tsukamoto, Hidekazu; Mann, Derek A.; Mann, Jelena

    2015-01-01

    Background and aims Alcohol is a primary cause of liver disease and an important co-morbidity factor in other causes of liver disease. A common feature of progressive liver disease is fibrosis, which results from the net deposition of fibril-forming extracellular matrix (ECM). The hepatic stellate cell (HSC) is widely considered to be the major cellular source of fibrotic ECM. We determined if HSC are responsive to direct stimulation by alcohol. Methods HSC undergoing transdifferentiation were incubated with ethanol and expression of fibrogenic genes and epigenetic regulators measured. Mechanisms responsible for recorded changes were investigated using ChIP-Seq and bioinformatics analysis. Ethanol induced changes were confirmed using HSCs isolated from mouse alcohol model, ALD patient liver and precision cut liver slices. Results HSCs responded to ethanol exposure by increasing profibrogenic and ECM gene expression including elastin. Ethanol induced altered expression of multiple epigenetic regulators indicative of a potential to modulate chromatin structure during HSC transdifferentiation. MLL1, a histone 3 lysine 4 (H3K4) methyltransferase, was induced by ethanol and recruited to the elastin gene promoter where it was associated with enriched H3K4me3, mark of active chromatin. Chromatin immunoprecipitation sequencing (ChIPseq) revealed that ethanol has broad effects on the HSC epigenome and identified 41 gene loci at which both MML1 and its H3K4me3 mark were enriched in response to ethanol. Conclusions Ethanol directly influences HSC transdifferentiation by stimulating global changes in chromatin structure resulting in increased expression of ECM proteins. The ability of alcohol to remodel epigenome during HSC transdifferentiation provides mechanisms for it to act as a comorbidity factor in liver disease. PMID:25457206

  14. Acute hepatitis B virus infection or acute exacerbation of chronic hepatitis B infection: the differential serological diagnosis.

    PubMed

    Pond, R A A

    2016-01-01

    Acute exacerbations of chronic hepatitis B are common, and may even be the first presentation of hepatitis B virus (HBV) infection. Sometimes, patients involved in these scenarios may have mistaken diagnosis of acute hepatitis B. The reason for the confusion is that the two forms of infection manifestation resemble remarkably in clinical, biochemical, and serological features, such as apparent rapid onset of severe disease, advanced grades of encephalopathy, high aminotransferases and prolonged international normalized ratios (INRs), as well as positivity for HBsAg and for IgM anti-HBc antibodies and DNA detection. Therefore, these two entities cannot be distinguished easily without historical information of HBV-associated chronic infection or recent HBV exposure, information that is often inaccurate. Considering the different prognoses, treatment strategies, and the epidemiological impact in the public health context, the correct diagnosis is extremely important. Despite the lack of effective and reliable tests to differentiate between acute infection and acute exacerbation of chronic HBV infection, the expression and kinetic evaluation of viral markers present in the circulation of individuals infected, the observation of physical-chemical properties of specific antibodies, and the combination of these findings represent some strategies in serology that could assist in differentiating between the two entities, or at least in the guidance for the correct diagnosis. PMID:26581426

  15. Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

    PubMed Central

    Perrin, H. Blasco; Cintas, P.; Abravanel, F.; Gérolami, R.; d'Alteroche, L.; Raynal, J.-N.; Alric, L.; Dupuis, E.; Prudhomme, L.; Vaucher, E.; Couzigou, P.; Liversain, J.-M.; Bureau, C.; Vinel, J.-P.; Kamar, N.; Izopet, J.

    2015-01-01

    Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection. PMID:26490255

  16. Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E.

    PubMed

    Perrin, H Blasco; Cintas, P; Abravanel, F; Grolami, R; d'Alteroche, L; Raynal, J-N; Alric, L; Dupuis, E; Prudhomme, L; Vaucher, E; Couzigou, P; Liversain, J-M; Bureau, C; Vinel, J-P; Kamar, N; Izopet, J; Peron, J-M

    2015-11-01

    Neurologic disorders, mainly Guillain-Barr syndrome and ParsonageTurner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barr syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection. PMID:26490255

  17. Improving Alcohol Withdrawal Outcomes in Acute Care

    PubMed Central

    Melson, Jo; Kane, Michelle; Mooney, Ruth; McWilliams, James; Horton, Terry

    2014-01-01

    Context Excessive alcohol consumption is the nations third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Objective: Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. Design: In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Main Outcome Measures: Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Results: Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%12.9%). In patients with DT, restraint use decreased (60.4%44.4%) and transfers to the ICU decreased (21.6%15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Conclusion: Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes. PMID:24867561

  18. Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

    PubMed

    Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

    2016-02-01

    Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. PMID:26790932

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

    PubMed

    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

    2015-08-01

    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 the acute phase of the infection. Currently used methods to diagnose acute HCV infection are IgG antibody seroconversion and repeated HCV RNA measurements, although no definitive diagnostic test is currently available. Progress in the field of adaptive and innate immune responses has aided both advances in the field of HCV vaccine development and a more basic understanding of viral persistence. The rapid changes in the treatment of chronic HCV infection will affect therapeutic regimens for acute HCV infection in the coming years, leading to shorter treatment courses and pegylated interferon-free modalities. This review gives an overview of the current knowledge and uncertainties, together with some future perspectives on acute hepatitis C epidemiology, virology, immunology, and treatment. PMID:25892133

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

    PubMed Central

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

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule out organic solvent-induced hepatitis. PMID:26735550

  1. [A case of acute pancreatitis and acute hepatitis caused by ingestion of Ceramium kondoi].

    PubMed

    Kim, Da-bin; Cho, Yoo-Kyung; Song, Hyun Joo; Song, Byung-Cheol

    2013-11-01

    In Korea, the use of herbal remedies is a common cause of drug-induced liver injury. However, the occurrence of both acute pancreatitis and acute hepatitis after taking herbal remedies has rarely been reported. Herein, we report a case of concurrent acute pancreatitis and acute hepatitis associated with Ceramium kondoi ingestion. A 58-year-old woman was diagnosed with advanced gastric cancer 7 months ago. Total gastrectomy and adjuvant chemotherapy was performed without complications. The patient had been well until recently, when she presented with severe abdominal pain after ingestion of Ceramium kondoifor 4 weeks. The laboratory findings demonstrated elevated liver enzymes and lipase, and abdominal computed tomography revealed pancreas swelling with fat infiltration. The diagnosis was made based on the diagnostic criteria for drug induced pancreatitis and the Russel Uclaf Causality Assessment Method scale for drug-induced liver injury. After cessation of Ceramium kondoi, she showed clinical and biochemical improvement. PMID:24262598

  2. CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis

    PubMed Central

    Affò, Silvia; Morales-Ibanez, Oriol; Rodrigo-Torres, Daniel; Altamirano, José; Blaya, Delia; Dapito, Dianne H; Millán, Cristina; Coll, Mar; Caviglia, Jorge M; Arroyo, Vicente; Caballería, Juan; Schwabe, Robert F; Ginès, Pere; Bataller, Ramón; Sancho-Bru, Pau

    2014-01-01

    Objective Chemokines are known to play an important role in the pathophysiology of alcoholic hepatitis (AH), a form of acute-on-chronic liver injury frequently mediated by gut derived lipopolysaccharide (LPS). In our study, we hypothesise that chemokine CCL20, one of the most upregulated chemokines in patients with AH, is implicated in the pathogenesis of AH by mediating LPS induced liver injury. Design CCL20 gene expression and serum levels and their correlation with disease severity were assessed in patients with AH. Cellular sources of CCL20 and its biological effects were evaluated in vitro and in vivo in chronic, acute and acute-on-chronic experimental models of carbon tetrachloride and LPS induced liver injury. RNA interference technology was used to knockdown CCL20 in vivo. Results CCL20 hepatic and serum levels were increased in patients with AH and correlated with the degree of fibrosis, portal hypertension, endotoxaemia, disease severity scores and short term mortality. Moreover, CCL20 expression was increased in animal models of liver injury and particularly under acute-on-chronic conditions. Macrophages and hepatic stellate cells (HSCs) were identified as the main CCL20 producing cell types. Silencing CCL20 in vivo reduced LPS induced aspartate aminotransferase and lactate dehydrogenase serum levels and hepatic proinflammatory and profibrogenic genes. CCL20 induced proinflammatory and profibrogenic effects in cultured primary HSCs. Conclusions Our results suggest that CCL20 upregulation is strongly associated with LPS and may not only represent a new potential biomarker to predict outcome in patients with AH but also an important mediator linking hepatic inflammation, injury and fibrosis in AH. PMID:24415562

  3. Hepatitis E virus in patients with acute severe liver injury

    PubMed Central

    Crossan, Claire Louise; Simpson, Kenneth J; Craig, Darren G; Bellamy, Christopher; Davidson, Janice; Dalton, Harry R; Scobie, Linda

    2014-01-01

    AIM: To examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit. METHODS: Hepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction. RESULTS: Four cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases. CONCLUSION: In patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history. PMID:25018853

  4. Non Alcoholic Fatty Liver Disease, Hepatic Insulin Resistance and Type 2 Diabetes

    PubMed Central

    Birkenfeld, Andreas L.; Shulman, Gerald I.

    2013-01-01

    Non alcoholic fatty liver disease (NAFLD), hepatic insulin resistance and type 2 diabetes are all strongly associated and are all reaching epidemic proportions. Whether there is a causal link between NAFLD and hepatic insulin resistance is controversial. This review will discuss recent studies in both humans and animal models of NAFLD that have implicated increases in hepatic diacylglycerol content leading to activation of PKCε resulting in decreased insulin signaling in the pathogenesis of NAFLD associated hepatic insulin resistance and type 2 diabetes. The DAG-PKCε hypothesis can explain the occurrence of hepatic insulin resistance observed in most cases of NAFLD associated with obesity, lipodystrophy and type 2 diabetes. PMID:23929732

  5. Acute hepatitis E virus infection and autoimmune thyroiditis: yet another trigger?

    PubMed Central

    Dumoulin, Franz Ludwig; Liese, Hanna

    2012-01-01

    A middle aged woman, previously healthy with the exception of mild seasonal asthma was presented with signs of acute hepatitis. The further investigation showed acute hepatitis E virus infection associated with autoimmune thyroiditis. Treatment was started with propranolol and carbimazol whereupon hepatitis and hyperthyroidism resolved. The authors think that the observed association of acute hepatitis E virus infection and autoimmune thyroiditis suggests a role of hepatitis E virus as putative trigger of autoimmune thyroiditis. The alternative possibility of thyroid dysfunction due to pre-existing autoantibodies cannot be completely excluded but seems to be unlikely given the very mild course of seasonal asthma in this patient. PMID:22604767

  6. Bidirectional interactions between acute psychosocial stress and acute intravenous alcohol in healthy men

    PubMed Central

    Childs, Emma; O'Connor, Sean; de Wit, Harriet

    2011-01-01

    Background The biological mechanisms by which acute stress increases alcohol consumption are unclear. One potential mechanism is that stress acts by altering the pharmacological and subjective effects of alcohol. Acute stress produces a cascade of physiological and psychological effects, each with a distinctive time course. In this study, we investigated whether different phases of response to an acute stress alter the subjective effects of intravenous alcohol, by administering the drug at two different times after the stress. Methods Healthy men (N=25) participated in two sessions; one with the Trier Social Stress Test, the other with a non-stressful control task, each followed by infusions of intravenous alcohol (targeting 40mg% in 5 min) and placebo. One group of participants received alcohol within 1 min of completing the tasks (Alc0, N=11), followed by placebo 30 min later. In the other group (Alc30, N=14), the order of alcohol and placebo infusions was reversed. Subjective effects (i.e., Anxiety, Stimulation, Want more) and physiological measures (heart rate, blood pressure, salivary cortisol) were measured before and at repeated intervals after the tasks and infusions. Results Stress did not change the subjective effects of alcohol in either group. However, when individual differences in alcohol responses were considered, stress differentially altered the stimulant-like and sedative effects of alcohol. Among individuals who exhibited predominantly stimulant responses to alcohol in the non-stressful condition, stress decreased the stimulant-like effects of alcohol and ‘wanting more’. By contrast, among participants who did not report stimulation after alcohol in the control session, stress decreased the sedative effects and increased ‘want more’. In addition, alcohol administered immediately after the TSST dampened cortisol responses yet prolonged negative subjective responses to the stress. Conclusions These findings demonstrate that there are bi-directional relationships between alcohol and stress. Alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual's pattern of response to alcohol. This study highlights the fact that stress-alcohol interactions vary among individual drinkers, suggesting that the effects of stress on motivation to drink alcohol may also differ between individuals. PMID:21762177

  7. Inpatient management of acute alcohol withdrawal syndrome.

    PubMed

    Perry, Elizabeth C

    2014-05-01

    Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as β-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751

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

    PubMed

    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 doxycycline for 14 days and became afebrile within four days. These cases were presented to emphasize that C.burnetii infection should be considered in the differential diagnosis of patients with fever and elevated serum transaminase levels, irrespective of the presence of abdominal pain and exposure to potentially infected animals. PMID:22951661

  9. [Hepatic steato-fibrosis and non-alcoholic liver disease in elderly].

    PubMed

    Mancinella, Angelo; Mancinella, Mirta; Marigliano, Benedetta; Marigliano, Vincenzo

    2012-05-01

    The critical role of the hepatic stellate cells in pathogenesis and evolution of hepatic fibrosis is stressed. The authors, also, illustrate the most recent acquisitions about morphological and bioumoral aspects of complex sinusoidal-Disse space-stellate cells and their importance for the risk of evolution towards non-alcoholic liver disease. PMID:22677947

  10. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  11. Maltol, a food flavoring agent, attenuates acute alcohol-induced oxidative damage in mice.

    PubMed

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  12. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    NASA Astrophysics Data System (ADS)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  13. Serodiagnosis of acute hepatitis B virus infection by a modified competitive binding radioimmunoassay.

    PubMed Central

    Schable, C A; Maynard, J E

    1982-01-01

    Using the Staphylococcus aureus absorption method, we have modified a commercial radioimmunoassay kit for the determination of total antibody to hepatitis B core antigen so that we can now determine the predominant globulin species of that antibody. One-hundred percent of acute hepatitis B sera had a predominance of immunoglobulin M antibody to hepatitis B core antigen, whereas immunoglobulin G antibody to hepatitis B core antigen was predominant in 98.2% of chronic hepatitis B surface antigen carriers. With this test and the commercially available tests for immunoglobulin M anti-hepatitis A virus, one can now reasonably differentiate acute hepatitis B from non A/non B hepatitis in a chronic hepatitis B surface antigen carrier. PMID:7153350

  14. [Biochemical markers for acute and chronic alcohol consumption].

    PubMed

    Geppert, Bogna; Tezyk, Artur; Zaba, Czesław

    2012-01-01

    In spite of the fact, that ethyl alcohol is a legal and socially accepted recreational drug its abuse may cause numerous problems for the individual and society. Casualties of car accidents caused by drunk drivers, aggressive behavior, family problems and effective less work are the main problems connected with alcohol abuse. The easiest and most effective way of proving recent alcohol consumption is confirming its presence in biological samples taken from the individual. However, the main disadvantage of this method is a short window detection for ethanol, because of its high speed of elimination process. Nowadays, in order to prevent and have a better control of alcohol abuse, markers that could provide a better view of short and long term ethanol consumption are in frequent use. Ethyl alcohol present in the body cause many qualitative and quantitative disturbances in biochemical metabolites that could be used as markers of its consumption. In practice markers of ethanol consumption are usually divided into acute (tests confirm single alcohol intake) and chronic (confirm long term alcohol consumption or lack of teetotalism). Markers of ethanol consumption are valuable alternative and complementation to customary examinations performed in medical practice and forensic medicine. PMID:23421117

  15. Acute Severe Hepatitis and Hemophagocytosis in Adult Onset Still's Disease.

    PubMed

    Sahutoglu, Tuncay; Kara, Elif; Dogan, Ibrahim Oner; Gulluoglu, Mine; Akyuz, Filiz; Besisik, Fatih

    2015-10-01

    We report a 44-year-old male Turkish patient with adult onset Still's disease (AOSD) complicated by acute severe hepatitis and hemophagocytosis. Initial investigations for fever and rapidly progressive elevation of liver function tests were not diagnostic. Routine evaluations of liver and bone marrow biopsies missed the fundamental pathology. Extremely elevated ferritin levels led to a more detailed search, and immunohistochemical staining with CD68 for macrophages revealed extensive hemophagocytosis in both the first and second bone marrow biopsies, as well as in the liver biopsy. Treatment with steroid and cyclosporine A induced complete remission. PMID:26443256

  16. Primary hepatic tuberculosis presenting as acute liver failure

    PubMed Central

    Jain, Deepak; Aggarwal, H. K.; Jain, Promil; Pawar, Sunil

    2014-01-01

    Abdominal tuberculosis is a common clinical entity in Indian subcontinent; however, hepatic tuberculosis in the absence of miliary abdominal tuberculosis is restricted to the case reports and small case series in English literature. It mimics common liver diseases like liver abscess and tumors. We report a case of 25-year-old immunocompetent female who presented with features of acute liver failure. Ultrasonography (USG) abdomen revealed multiple hypoechoic lesions. However, patient expired within 48 h of presentation but her liver autopsy revealed multiple epithelioid cell caseating granulomas with positive staining for acid fast bacilli (AFB). Polymerase chain reaction (PCR) was also positive for Mycobacterium tuberculosis. PMID:25988063

  17. Acute Hepatic Phenotype of Wilson Disease: Clinical Features of Acute Episodes and Chronic Lesions Remaining in Survivors

    PubMed Central

    Hayashi, Hisao; Tatsumi, Yasuaki; Yahata, Shinsuke; Hayashi, Hiroki; Momose, Kenji; Isaji, Ryohei; Sasaki, Youji; Hayashi, Kazuhiko; Wakusawa, Shinya; Goto, Hidemi

    2015-01-01

    Background and Aims: Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease. Methods: Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines. Results: All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure. Conclusions: All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD. PMID:26807378

  18. Recent epidemiological and clinical features of acute hepatitis B in a single center of China

    PubMed Central

    Chen, Xiaohong; Fu, Chengtao; Liu, Jia; Shan, Lei; Liu, Chenglin

    2015-01-01

    Aim: This study was to investigate the epidemiological and clinical features of acute hepatitis B. Methods: A retrospective study of 177 acute hepatitis B patients with an average age of 36.03 years and range of 7-62 years was conducted from Jan 2005 to Feb 2011. The epidemiological and clinical parameters were investigated. The serological markers and biochemical tests were examined. Results: 76.84% (n = 136) patients were icteric type, while 23.16% (n = 41) were non-icteric type. Other clinical manifestations for acute hepatitis patients included fatigue (82.49%), gastrointestinal symptoms (66.10%), yellowish discoloration of skin and sclera, fever (31.07%), rash 10 (5.65%), joint pain (2.82%) and headache (1.69%). One case presented with acute renal failure associated with acute hepatitis B. Nine cases suffered from fulminant hepatitis. After treatment, hepatic function was significantly improved (P < 0.05). For serological markers, 54 (30.51%) and 119 (67.23%) patients had HBsAg and HBV-DNA seroconversion respectively. Four deaths occurred due to the severe complications associated by acute infection of HBV during half a year period follow up. Conclusions: Adult males with occupation of workers and farmers are the high-risk population of acute hepatitis B in China. Several complications associated with acute hepatitis B should be noticed. PMID:26629198

  19. Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

    PubMed Central

    Tsai, Wei-Lun; Sun, Wei-Chi; Cheng, Jin-Shiung

    2015-01-01

    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(t)ide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(t)ide 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. PMID:26703566

  20. Safety of general anaesthesia and surgery in acute hepatic porphyria.

    PubMed Central

    Dover, S B; Plenderleith, L; Moore, M R; McColl, K E

    1994-01-01

    Patients with acute hepatic porphyria are denied essential operations because of concern that general anaesthesia and surgery will precipitate a life threatening porphyric crisis. This study assessed the safety of surgery under general anaesthesia in these patients. A combined prospective and retrospective case note study, with a biochemical study, was conducted in 25 patients with acute hepatic porphyria undergoing 38 surgical operations. Clinical outcome measures were survival and occurrence of porphyric crisis after surgery. The biochemical activity of porphyria was assessed by measurement of the perioperative 24 hour excretion of the haem precursors delta amino-laevulinic acid (ALA) and porphobilinogen (PBG). There were no deaths or crises after 29 operations in 19 patients who were known to have porphyria before their surgery, and therefore given only appropriate drugs. These operations include such major procedures as mitral valve replacement, hip replacement, coronary artery grafting, cholecystectomies, and renal transplantation. In eight of these patients the urinary excretion of ALA and PBG were studied, and showed no sustained postoperative increase. Nine operations were performed in eight patients before the diagnosis of porphyria was known and who thus received routine anaesthetic agents. Seven of these patients developed a postoperative porphyric crisis. Two of them died. It is concluded therefore that even the most major surgery can be undertaken safely in patients with porphyria. The risk is for undiagnosed cases. PMID:7926916

  1. [Effect of alcohol on organ microcirculation: its relation to hepatic, pancreatic and gastrointestinal diseases due to alcohol].

    PubMed

    Horie, Y; Ishii, H

    2001-10-01

    Although alcohol is well recognized as a systemic toxin, the enteric manifestations of alcohol abuse have only recently begun to be elucidated at the cellular and microvascular levels. Since the microvascular mechanism of the toxicity of alcohol has progressively been revealed, clinical applications of this research field should increase the availability of therapeutic options for alcohol-induced injuries of liver, pancreas and gastrointestinal (GI) tract. A high concentration of ethanol reduces GI and pancreas blood flow. Ethanol-induced GI hemorrhage, GI ulcer, and pancreatitis are initiated by the microcirculatory disturbance of GI mucosa and pancreas. Ethanol administration induces an increase in vasoactive agents such as endothelin and nitric oxide and oxidative stress. They appear to be involved in ethanol-induced GI and pancreatic injury. Regarding the effects of ethanol on the liver, small amount of ethanol increases hepatic blood flow, and prevents gut ischemia/reperfusion (I/R)-induced hepatic microvascular dysfunction and subsequent liver injury. While large amount of ethanol itself causes hepatic microvascular dysfunction, and aggravates the gut I/R-induced hepatic microvascular dysfunction and subsequent liver injury. Vasoactive agents and oxidative stress also appear to be involved in the liver injury. In endotoxemic animals, even small amount of ethanol causes hepatic microvascular dysfunction. Chronic ethanol consumption aggravates endotoxin-induced hepatic microvascular dysfunction. Chronic ethanol consumption aggravates gut I/R-induced leukostasis in the liver and hepatocellular injury associated with an enhanced expression of adhesion molecules, while it prevents the gut I/R-induced sinusoidal perfusion injury. Thus, effects of chronic ethanol consumption on the I/R injury are still controversial. PMID:11725532

  2. Drug and alcohol abuse in patients with acute burn injuries.

    PubMed

    Swenson, J R; Dimsdale, J E; Rockwell, E; Carroll, W; Hansbrough, J

    1991-01-01

    We reviewed records of adult patients admitted to our burn unit who were reported to abuse drugs or alcohol from 1985 to 1988. The proportion of patients reported as abusing drugs increased significantly from 1987 to 1988, compared to previous years. However, there was no increase in the proportion of patients reported to abuse alcohol. Patients identified as abusing drugs had longer hospital stays, compared to patients who were not reported to abuse substances. Methamphetamine and cocaine were the drugs most often abused by patients who abused drugs or both drugs and alcohol. Mechanisms of burn injury in these patients included "accidental" burn injury related to acute intoxication, and self-injury due to psychosis or depression. PMID:1882020

  3. Erythropoietic and hepatic porphyrias.

    PubMed

    Gross, U; Hoffmann, G F; Doss, M O

    2000-11-01

    Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased metabolites upstream of the enzymatic defect are excreted into urine and faeces. The diagnosis is based on their evaluation. Primary enzymatic or molecular analyses are noncontributary and may be misleading. Acute polysymptomatic exacerbations accompany a high excretory constellation of porphyrin precursors delta-aminolaevulinic acid and porphobilinogen. Homozygous or compound heterozygous variants of acute hepatic porphyrias may already manifest in childhood. PMID:11117426

  4. Alcohol Deranges Hepatic Lipid Metabolism via Altered Transcriptional Regulation.

    PubMed Central

    Crabb, David W.

    2004-01-01

    Alcohol has classically been thought to cause fatty liver by way of altered redox potential in the liver, which inhibits fatty acid oxidation. Additional effects appear to play a role both in impairing fat oxidation and stimulating lipogenesis. Alcohol reduces the DNA binding and transcription-activating properties of peroxisome proliferator-activated receptor alpha (PPARalpha), both in cultured cells and in mice fed alcohol. Treatment of alcohol-fed mice with a PPARalpha agonist reverses fatty liver despite continued alcohol consumption. Alcohol also activates sterol response element- binding protein 1 (SREBP-1), inducing a battery of lipogenic enzymes. This effect may be due in part to inhibition of AMP-dependent protein kinase. This understanding of alcohol effects provides new therapeutic targets to reverse alcoholic fatty liver. Images Fig. 4 Fig. 6 PMID:17060973

  5. Clinical recurrence of hepatitis A following liver transplantation for acute liver failure.

    PubMed

    Gane, E; Sallie, R; Saleh, M; Portmann, B; Williams, R

    1995-01-01

    This paper documents clinically significant recurrence of hepatitis A virus (HAV) infection in a 63-year-old man transplanted for HAV-related acute liver failure. HAV RNA was documented in the explant and, following early clearance from the blood and graft, was again detected in post-operative biopsies at the time of an acute hepatic illness. Although the clinical and biochemical abnormalities resolved completely, the patient had a second episode of graft dysfunction 6 months later and investigations revealed hepatitis C virus (HCV)-related chronic active hepatitis consistent with acquired HCV infection at the time of transplantation. The possible interaction with hepatitis A may have delayed the appearance of hepatitis C. Administration of HAV immunoglobulin at the time of transplantation should be considered in all cases of HAV-related fulminant hepatic failure. PMID:7714491

  6. Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which is associated with hepatocarcinogenesis. We investigated whether treatment with chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated hepatic carcinogenesis in rats. Rats were fed either an ethan...

  7. Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis

    PubMed Central

    Ascha, Mona; Wang, Zeneng; Ascha, Mustafa S; Dweik, Raed; Zein, Nizar N; Grove, David; Brown, J Mark; Marshall, Stephanie; Lopez, Rocio; Hanouneh, Ibrahim A

    2016-01-01

    AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis (AH). METHODS: We prospectively recruited patients with cirrhosis from AH (n = 23) and those with cirrhosis with acute decompensation (AD) from etiologies other than alcohol (n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival. RESULTS: A comparison of model for end-stage liver disease (MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD (area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54 (0.18, 0.91); P = 0.005], homocitrulline [0.66 (0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53 (0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers (carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION: Metabolomics plasma analyte levels might be used to diagnose of AH or help predict patient prognoses. PMID:27057307

  8. HEV Infection as an Aetiologic Factor for Acute Hepatitis: Experience from a Tertiary Hospital in Bangladesh

    PubMed Central

    Rahman, Salimur; Khan, Mobin; Karim, Fazal

    2009-01-01

    Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004–December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 μmol/L, raised serum transaminases, and prothrombin time ≥3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in cirrhotics in Bangladesh. Sewerage contamination of piped water following floods may contribute to the higher incidence of HEV infection. PMID:19248644

  9. Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes.

    PubMed

    Wang, Junming; Zhang, Yueyue; Liu, Ruixin; Li, Xiaobing; Cui, Ying; Qu, Lingbo

    2015-04-01

    Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver. PMID:25730420

  10. Hepatitis E and Acute Liver Failure in Pregnancy

    PubMed Central

    Shalimar; Acharya, Subrat K.

    2013-01-01

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

  11. Hepatitis e and acute liver failure in pregnancy.

    PubMed

    Shalimar; Acharya, Subrat K

    2013-09-01

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

  12. Acute liver failure caused by severe acute hepatitis B: a case series from a multi-center investigation

    PubMed Central

    2014-01-01

    Background Few data can be available regarding acute liver failure (ALF) caused by severe acute hepatitis B up to now. This study aims to report such cases from China. Findings We conducted a multi-center investigation on ALF from 7 tertiary hospitals in different areas of China. A total of 11 patients with ALF caused by severe acute hepatitis B were finally identified. In these patients, there were 10 male and 1 female patients. As a serious complication, apparent hemorrhage occurred in 9 patients. Eventually, in these 11 patients, 4 survived and 7 died. 4 died of heavy bleeding, 2 died of systemic inflammatory response syndrome and 1 died of irreversible coma. No patients received liver transplantation. Conclusions ALF caused by severe acute hepatitis B is worthy of formal studies based on its rarity and severity. PMID:24958233

  13. Ligustrazine prevents alcohol-induced liver injury by attenuating hepatic steatosis and oxidative stress.

    PubMed

    Lu, Chunfeng; Xu, Wenxuan; Zhang, Feng; Jin, Huanhuan; Chen, Qin; Chen, Lianyun; Shao, Jiangjuan; Wu, Li; Lu, Yin; Zheng, Shizhong

    2015-12-01

    Alcoholic liver disease (ALD) is a major etiology of liver diseases, causing heavy health burdens personally and socially. Ligustrazine has been widely used in China due to its extensive pharmacological activities. However, the role of ligustrazine in ALD treatment remains unclear. Thus, this study is aimed to make up this gap and further uncover the potential mechanisms. The present work demonstrated that compared with the alcohol feeding group, ligustrazine-treated groups showed a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities in serum, and a great improvement in liver histology. Additionally, ligustrazine reduced the number of foci containing CD45 positive cells and the expression of proteins associated with hepatic inflammation, apoptosis, and fibrosis. Further, ligustrazine obviously abolished alcohol-induced hepatic steatosis and hyperlipidemia. In addition, ligustrazine reversed alcohol-induced overexpression of sterol regulatory element-binding protein-1c and fatty acid synthase, and inhibition of peroxisome proliferator-activated receptor-alpha and carnitine palmitoyltransferase 1 in liver. Ligustrazine also ameliorated alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and decreases in glutathione, superoxide dismutase, catalase, and glutathione reductase content in liver. Finally, chronic alcohol feeding inhibited the hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf2) at both mRNA and protein levels. Ligustrazine promoted Nrf2 expression and nuclear translocation in a dose-dependent manner. Collectively, for the first time, the present study demonstrated that ligustrazine remarkably improved chronic alcohol-induced liver injury by attenuating hepatic steatosis and oxidative stress. Further, Nrf2 activation might be requisite for ligustrazine to exert its protective effects. PMID:26459052

  14. Cardiorenal syndrome followed by acute hepatitis C in a patient with acute myeloid leukemia

    PubMed Central

    Mihaila, Romeo-Gabriel

    2014-01-01

    Cardiorenal syndrome involves altering cardiac and renal function. These patients frequently develop resistance to diuretic therapy, so that ultrafiltration should be applied in emergency for saving them. Concomitant presence of an active hematologic malignancy represents an important complicating factor. We present the case of an elderly patient with acute myeloid leukemia, appeared on the background of myelodysplastic syndrome who, during marrow aplasia occurred after the first course of induction chemotherapy, developed a cardiorenal syndrome, which required repeated sessions of hemodialysis. Complete hematologic remission and efficiency of fluid depletion therapy allowed the second course of polychemotherapy, after which the patient developed an acute hepatitis C. After 8 months of complete hematologic remission that persists, the patient will be put on the standard antivirusologic treatment. PMID:24949003

  15. Alcohol and porphyrin metabolism.

    PubMed

    Doss, M O; Kühnel, A; Gross, U

    2000-01-01

    Alcohol is a porphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive consumption of alcohol, a temporary, clinically asymptomatic secondary hepatic coproporphyrinuria is observable, which can become persistent in cases of alcohol-induced liver damage. Nowadays, the alcohol-liver-porphyrinuria syndrome is the first to be mentioned in secondary hepatic disturbances of porphyrin metabolism. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are considered to be molecular regulatory diseases, in contrast to non-acute, chronic hepatic porphyria, clinically appearing as porphyria cutanea tarda (PCT). Porphyrins do not accumulate in the liver in acute porphyrias, whereas in chronic hepatic porphyrias they do. Thus, chronic hepatic porphyria is a porphyrin-accumulation disease, whereas acute hepatic porphyrias are haem-pathway-dysregulation diseases, characterized in general by induction of delta-aminolevulinic acid synthase in the liver and excessive stimulation of the pathway without storage of porphyrins in the liver. The clinical expression of acute hepatic porphyrias can be triggered by alcohol, because alcohol augments the inducibility of delta-aminolevulinic acid synthase. In chronic hepatic porphyrias, however, which are already associated with liver damage, alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Especially in persons with a genetic deficiency of uroporphyrinogen decarboxylase, but also in patients with the so-called sporadic variety of PCT, alcohol is able to transform an asymptomatic coproporphyrinuria into PCT. Alcohol has many biochemical and clinical effects on porphyrin and haem synthesis both in humans and laboratory animals. Ethanol suppresses the activity of porphobilinogen synthase (synonym: delta-aminolevulinic acid dehydratase), uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase, whereas it induces the first and rate-limiting enzyme in the pathway, delta-aminolevulinic acid synthase and also porphobilinogen deaminase. Therefore, teetotalism is a therapeutically and prophylactically important measure in all types of hepatic porphyrias. PMID:10787385

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

    PubMed

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

    2014-11-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the King's College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and recovered. Careful investigation identified imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010 affecting 13 patients. Virus sequence analysis of our patient's virus showed a strain commonly found in Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute liver failure, and hepatitis A vaccine. PMID:25195154

  17. Liver transplantation for acute liver failure related to autochthonous genotype 3 hepatitis E virus infection.

    PubMed

    Aherfi, Sarah; Borentain, Patrick; Raissouni, Ferdaous; Le Goffic, Aude; Guisset, Michel; Renou, Christophe; Grimaud, Jean-Charles; Hardwigsen, Jean; Garcia, Stéphane; Botta-Fridlund, Danielle; Nafati, Cyril; Motte, Anne; Le Treut, Yves Patrice; Colson, Philippe; Gerolami, René

    2014-02-01

    Hepatitis E virus of genotype 3 (HEV-3) is an emerging cause of sporadic autochthonous acute hepatitis in Europe. Although spontaneous outcome of hepatitis E is usually favorable, fulminant liver failure has been described worldwide. In Europe, autochthonous hepatitis E associated with fulminant hepatic failure and leading to liver transplantation has been exceptionally reported. We report here four cases of fulminant and sub-fulminant hepatitis E proposed for liver transplantation in Marseille University hospitals between July 2006 and March 2010. HEV diagnosis relied on detection of anti-HEV IgM antibodies and HEV RNA in serum samples. All cases were men, with no travel history in hyperendemic areas. HEV sequence analyses revealed genotype 3 HEV in the four patients. Liver histology indicated severe acute hepatitis in all of them, pre-existing fibrosis being found in two cases. Two patients underwent liver transplantation, and the two other patients could not be transplanted due to septic complications and died. HEV testing should be performed for the initial evaluation of every acute liver failure regardless of the epidemiological and clinical context. With respect to the potentially fulminant evolution of HEV genotype 3 infections, treatment with ribavirin of severe acute hepatitis E should be considered. PMID:24462173

  18. Gas in Hepatic Portal Veins with Gastric Massive Dilatation and Pneumatosis in Acute Pancreatitis

    PubMed Central

    Mushtaq, Nadeem; Pateria, Vibhor; Ahmad, Imtiyaz; Kulshreshtha, Nitin

    2015-01-01

    Gas in portal veins is a rare phenomenon observed secondary to bowel ischaemia and necrosis. A young girl with history of pica ingestion presented with acute abdomen with huge distension. Investigation revealed air in hepatic portal veins, air within stomach wall, and massive distension of stomach secondary to acute pancreatitis. Successful conservative treatment confirmed the current concept that all cases of hepatic portal venous gas do not warrant immediate surgical intervention. PMID:26557565

  19. Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic haemochromatosis from alcoholic liver disease complicated by alcoholic haemosiderosis.

    PubMed

    Sallie, R W; Reed, W D; Shilkin, K B

    1991-02-01

    The hepatic tissue iron index proposed by Bassett et al was evaluated in 35 patients with homozygous genetic haemochromatosis, 67 patients with alcoholic liver disease, and 18 patients with other forms of chronic liver disease with and without cirrhosis. In patients with cirrhosis hepatic tissue iron concentration reliably differentiated alcoholic liver disease from genetic haemochromatosis. Although mean iron concentration was greater in patients with prefibrotic haemochromatosis than in those with prefibrotic alcoholic liver disease, some overlap occurred and complete differentiation of the two conditions was not possible. This overlap was particularly evident in some young patients with haemochromatosis in whom the tissue iron concentration grade fell in the range commonly seen in alcoholic haemosiderosis. Inability to differentiate early genetic haemochromatosis from alcoholic liver disease complicated by haemosiderosis was also a problem with standard Perls's staining. When the hepatic tissue iron index was calculated (hepatic tissue iron concentration/patient's age in years), clear differentiation of genetic haemochromatosis from both alcoholic liver disease and other forms of chronic liver disease was obtained in both cirrhotic and precirrhotic patients. This study confirms that the hepatic tissue iron index is a useful means of differentiating patients with genetic haemochromatosis from those with alcoholic liver disease. We suggest that biochemical estimation of tissue iron concentration and calculation of the tissue iron index in all patients in whom genetic haemochromatosis is a possible diagnosis will reduce the likelihood of misdiagnosing this as alcoholic liver disease. PMID:1864543

  20. Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function

    SciTech Connect

    Lieber, Charles S. Leo, Maria Anna; Wang, Xiaolei; DeCarli, Leonore M.

    2008-08-22

    Chronic alcohol consumption affects the gene expression of a NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-{gamma} coactivator1{alpha} (PGC-1{alpha}). Our aim was to verify that it also alters the forkhead (FoxO1) and p53 transcription factor proteins, critical in the hepatic response to oxidative stress and regulated by SIRT1 through its deacetylating capacity. Accordingly, rats were pair-fed the Lieber-DeCarli alcohol-containing liquid diets for 28 days. Alcohol increased hepatic mRNA expression of FoxO1 (p = 0.003) and p53 (p = 0.001) while corresponding protein levels remained unchanged. However phospho-FoxO1 and phospho-Akt (protein kinase) were both decreased by alcohol consumption (p = 0.04 and p = 0.02, respectively) while hepatic p53 was found hyperacetylated (p = 0.017). Furthermore, mitochondrial SIRT5 was reduced (p = 0.0025), and PGC-1{alpha} hyperacetylated (p = 0.027), establishing their role in protein modification. Thus, alcohol consumption disrupts nuclear-mitochondrial interactions by post-translation protein modifications, which contribute to alteration of mitochondrial biogenesis through the newly discovered reduction of SIRT5.

  1. Dysregulation of hepatic zinc transporters in a mouse model of alcoholic liver disease

    PubMed Central

    Sun, Qian; Li, Qiong; Zhong, Wei; Zhang, Jiayang; Sun, Xiuhua; Tan, Xiaobing; Yin, Xinmin; Sun, Xinguo; Zhang, Xiang

    2014-01-01

    Zinc deficiency is a consistent phenomenon observed in patients with alcoholic liver disease, but the mechanisms have not been well defined. The objective of this study was to determine if alcohol alters hepatic zinc transporters in association with reduction of hepatic zinc levels and if oxidative stress mediates the alterations of zinc transporters. C57BL/6 mice were pair-fed with the Lieber-DeCarli control or ethanol diets for 2, 4, or 8 wk. Chronic alcohol exposure reduced hepatic zinc levels, but increased plasma and urine zinc levels, at all time points. Hepatic zinc finger proteins, peroxisome proliferator-activated receptor-α (PPAR-α) and hepatocyte nuclear factor 4α (HNF-4α), were downregulated in ethanol-fed mice. Four hepatic zinc transporter proteins showed significant alterations in ethanol-fed mice compared with the controls. ZIP5 and ZIP14 proteins were downregulated, while ZIP7 and ZnT7 proteins were upregulated, by ethanol exposure at all time points. Immunohistochemical staining demonstrated that chronic ethanol exposure upregulated cytochrome P-450 2E1 and caused 4-hydroxynonenal accumulation in the liver. For the in vitro study, murine FL-83B hepatocytes were treated with 5 μM 4-hydroxynonenal or 100 μM hydrogen peroxide for 72 h. The results from in vitro studies demonstrated that 4-hydroxynonenal treatment altered ZIP5 and ZIP7 protein abundance, and hydrogen peroxide treatment changed ZIP7, ZIP14, and ZnT7 protein abundance. These results suggest that chronic ethanol exposure alters hepatic zinc transporters via oxidative stress, which might account for ethanol-induced hepatic zinc deficiency. PMID:24924749

  2. [Physical diseases in alcoholism].

    PubMed

    Takase, Kojiro

    2015-09-01

    Rapid excessive alcohol drinking frequently causes disturbance of consciousness due to head trauma, brain edema, hypoglycemia, hyponatremia, hepatic coma and so on, provoked by acute alcohol intoxication. Rapid differential diagnosis and management are extremely important to save a life. On the other hands, the chronic users of alcohol so called alcoholism has many kinds of physical diseases such as liver diseases (i.e., fatty liver, alcoholic hepatitis, alcoholic liver cirrhosis and miscellaneous liver disease), diabetes mellitus, injury to happen in drunkenness, pancreas disease (i.e., acute and chronic pancreatitis and deterioration of chronic pancreatitis), gastrontestinal diseases (i.e., gastroduodenal ulcer), and so on. Enough attention should be paid to above mentioned diseases, otherwise they would turn worse more with continuation and increase in quantity of the alcohol. It should be born in its mind that the excessive drinking becomes the weapon threatening life. PMID:26394519

  3. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice

    PubMed Central

    Deshpande, Krutika T.; Liu, Shinlan; McCracken, Jennifer M.; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N.; Richard, Zachary C.; O’Neil, Maura F.; Pritchard, Michele T.

    2016-01-01

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure. PMID:26751492

  4. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.

    PubMed

    Deshpande, Krutika T; Liu, Shinlan; McCracken, Jennifer M; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N; Richard, Zachary C; O'Neil, Maura F; Pritchard, Michele T

    2016-01-01

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl₄-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl₄ exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl₄ and euthanized 24-96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl₄-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl₄ exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl₄-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl₄. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure. PMID:26751492

  5. [Prevalence of hepatitis C virus and excessive consumption of alcohol in a nonhospital worker population].

    PubMed

    Prieto Domingo, J J; Carrión Bolaños, J A; Bandrés Moya, F

    1997-12-01

    The aim of the study was to know the prevalence of the hepatitis C virus (HCV) in a non hospital work population by ELISA 3.0 and PCR-Amplicor, as well as its relationship with excessive alcohol intake (more than 280 g/week in men and 168 g/week in women). A transversal seroepidemiologic study was carried out in 1,109 workers of the Empresa Nacional de Electricidad, S.A. (ENDESA). During the annual medical examinations (April 1993-October 1994) the amount of alcoholic beverages each worker had consumed over the 7 days prior to the medical examination was obtained by anamnesis together with a blood sample for different laboratory tests. Sixteen percent of the workers had had excessive alcohol intake. The prevalence of anti HCV antibodies in the study population was 2.4% being up to 4.6% in the workers declaring excessive alcohol consumption and 10.4% if they also presented an elevation in any of the transaminases. The prevalence of the potentially ineffective workers was 1.46%. The prevalence of anti C antibodies by ELISA 3.0 was greater than expected (2.4%) significantly increasing in the population group which declared excessive alcohol intake, thereby demonstrating the relationship between alcohol and hepatitis C. PMID:9580041

  6. Chunggan extract, a traditional herbal formula, ameliorated alcohol-induced hepatic injury in rat model

    PubMed Central

    Kim, Hyeong-Geug; Kim, Jung-Min; Han, Jong-Min; Lee, Jin-Seok; Choi, Min-Kyung; Lee, Dong-Soo; Park, Yeon-Hwa; Son, Chang-Gue

    2014-01-01

    AIM: To evaluate protective effects of Chunggan extract (CGX), a traditional herbal formula, under 4 wk of alcohol consumption-induced liver injury. METHODS: Male Sprague-Dawley Rats were orally administered 30% ethanol daily for 4 wk with or without CGX. The pharmaceutical properties were assessed through liver enzymes, histopathology, fibrogenic cytokines, and alcohol metabolism in hepatic tissues as well as by in vitro experiment using HSC-T6 cells. RESULTS: Four weeks of alcohol consumption notably increased liver enzymes and malondialdehyde levels in serum and hepatic tissue. CGX not only prevented the collagen deposition determined by histopathology and hydroxyproline content, but also normalized transforming growth factor-beta, platelet-derived growth factor-beta and connective tissue growth factor at the gene expression and protein levels in liver tissue. Moreover, CGX treatment also significantly normalized the abnormal changes in gene expression profiles of extracellular matrix proteins, matrix metalloproteinase and their inhibitors, alcohol metabolism, and inflammatory reactions. In the acetaldehyde-stimulated HSC-T6 cells, CGX considerably inhibited collagen production and normalized fibrogenic cytokines in both gene expression and protein levels. CONCLUSION: The present study evidenced that CGX has hepatoprotective properties via modulation of fibrogenic cytokines and alcohol metabolism in alcoholic liver injury. PMID:25400454

  7. High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise

    PubMed Central

    Charbonneau, Alexandre; Unson, Cecilia G; Lavoie, Jean-Marc

    2007-01-01

    Studies have revealed that high-fat (HF) diets promote hyperglycaemia, whole-body insulin resistance and non-alcoholic fatty liver disease (NAFLD). Recently, hepatic glucagon resistance has been shown to occur in rats fed a HF diet. More precisely, diet-induced obesity (DIO) reduces the number of hepatic plasma membrane glucagon receptors (GR), which results in a diminished response to glucagon during a hyperglucagonaemic clamp. The present study was undertaken to test the hypothesis that a HF-DIO is associated with a desensitization and destruction of the hepatic GR. We also hypothesized that a single bout of endurance exercise would modify the GR cellular distribution under our DIO model. Male rats were either fed a standard (sd) or a HF diet for two weeks. Each group was subdivided into a non-exercised (Rest) and an acute exercised (EX) group. The HF diet resulted in a reduction of total hepatic GR (55%) and hepatic plasma membrane GR protein content (20%). These changes were accompanied by a significant increase in endosomal and lysosomal GR content with the feeding of a HF diet. The reduction of GR plasma membrane as well as the increase in endosomal GR was strongly correlated with an increase of PKC-α, suggesting a role of PKC-α in GR desensitization. EX increased significantly PKC-α protein content in both diets, suggesting a role of PKC-α in EX-induced GR desensitization. The present results suggest that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in total cellular and plasma membrane GR content. Furthermore, the GR desensitization observed in our in vivo model of HF diet-induced hepatic steatosis and in EX individuals may be regulated by PKC-α. PMID:17053032

  8. Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis

    PubMed Central

    Osna, Natalia A; Thomes, Paul G; Jr, Terrence M Donohue

    2011-01-01

    This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracellular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers. PMID:21633655

  9. Hepatic non-parenchymal cells: Master regulators of alcoholic liver disease?

    PubMed Central

    Seo, Wonhyo; Jeong, Won-Il

    2016-01-01

    Chronic alcohol consumption is one of the most common causes of the progression of alcoholic liver disease (ALD). In the past, alcohol-mediated hepatocyte injury was assumed to be a significantly major cause of ALD. However, a huge number of recent and brilliant studies have demonstrated that hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and diverse types of lymphocytes play crucial roles in the pathogenesis of ALD by producing inflammatory mediators such as cytokines, oxidative stress, microRNA, and lipid-originated metabolites (retinoic acid and endocannabinoids) or by directly interacting with parenchymal cells (hepatocytes). Therefore, understanding the comprehensive roles of hepatic non-parenchymal cells during the development of ALD will provide new integrative directions for the treatment of ALD. This review will address the roles of non-parenchymal cells in alcoholic steatosis, inflammation, and liver fibrosis and might help us to discover possible therapeutic targets and treatments involving modulating the non-parenchymal cells in ALD. PMID:26819504

  10. Hepatic non-parenchymal cells: Master regulators of alcoholic liver disease?

    PubMed

    Seo, Wonhyo; Jeong, Won-Il

    2016-01-28

    Chronic alcohol consumption is one of the most common causes of the progression of alcoholic liver disease (ALD). In the past, alcohol-mediated hepatocyte injury was assumed to be a significantly major cause of ALD. However, a huge number of recent and brilliant studies have demonstrated that hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and diverse types of lymphocytes play crucial roles in the pathogenesis of ALD by producing inflammatory mediators such as cytokines, oxidative stress, microRNA, and lipid-originated metabolites (retinoic acid and endocannabinoids) or by directly interacting with parenchymal cells (hepatocytes). Therefore, understanding the comprehensive roles of hepatic non-parenchymal cells during the development of ALD will provide new integrative directions for the treatment of ALD. This review will address the roles of non-parenchymal cells in alcoholic steatosis, inflammation, and liver fibrosis and might help us to discover possible therapeutic targets and treatments involving modulating the non-parenchymal cells in ALD. PMID:26819504

  11. Trends of Acute Hepatitis B Notification Rates in Eastern China from 2005 to 2013

    PubMed Central

    Wang, Zhifang; Chen, Yaping; Pan, Jinren

    2014-01-01

    Zhejiang Province was a high endemicity for hepatitis B disease in the 1990's. A number of measures implemented since then have begun to control and prevent hepatitis B. In 1992, hepatitis B vaccine came on the market. In 2002, hepatitis B vaccine was included in the national Expanded Programme on Immunization (EPI). Between 2007 and 2010, catch-up vaccination was implemented for children under 15. Since 2010, vaccination guidelines for high-risk groups have also been adopted. This study evaluated the impact of these control and prevention strategies on acute hepatitis B notification rates from 2005 through 2013. Data from the National Notifiable Disease Reporting System (NNDRS) revealed a steady downward trend in notification rates of acute hepatitis B. The most dramatic decline occurred among pre-adults, highlighting the benefits of EPI's policy of universal vaccination for children. However, the highest notification rates occurred among young adults of lower socio-economic status. These findings indicate the strong need to vaccinate young adults at risk for HBV infection as well as to collect risk-factor information in the NNDRS for monitoring and following up persons with acute hepatitis B. PMID:25504088

  12. Acute acalculous cholecystitis caused by Hepatitis C: A rare case report

    PubMed Central

    Omar, Ahmed; Osman, Medhet; Bonnet, Gerard; Ghamri, Nafiz

    2015-01-01

    Introduction Acute acalculous cholecystitis (AAC) is rarely encountered in clinical practice and has a high morbidity and mortality. AAC caused by viral hepatitis, with hepatitis A, B and EBV infections are rare, but well documented in the literature. Hepatitis C virus has not been reported as cause of AAC. This case report documents the first case of AAC associated with Acute Hepatitis C. Presenting concerns We present a 40 years old female with abdominal pain. She has a history of previous HCV infection. Her liver function tests were markedly deranged with elevated inflammatory markers. USS scan showed rather a very unusual appearance of an inflamed gallbladder with no gallstones and associated acute hepatitis, confirmed by an abdominal CT scan. HCV RNA PCR confirms flair up of the virus. The patient was managed conservatively in the hospital with follow up USS scan and Liver function tests showed complete recovery. Follow up HCV RNA PCR also returned to an undetectable level. The patient recovered completely with no adverse outcomes. Conclusion This case report is to the first to document the association between acute HCV and AAC. Despite being uncommon in western countries, viral hepatitis should be suspected as a causative agent of AAC, particularly when there is abnormal liver function test and no biliary obstruction. PMID:26722714

  13. Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B.

    PubMed

    Su, Feifei; Dai, Jianyi; Yang, Shoufeng; Jiang, Xiangao; Cui, Xiaoya; Ning, Hongye; Li, Junhua; Huang, Mohe

    2015-09-01

    The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B. PMID:26032700

  14. The effects of acute alcohol administration on the human brain: insights from neuroimaging.

    PubMed

    Bjork, James M; Gilman, Jodi M

    2014-09-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. PMID:23978384

  15. The effects of acute alcohol administration on the human brain: Insights from neuroimaging

    PubMed Central

    Bjork, James M.; Gilman, Jodi M.

    2014-01-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. PMID:23978384

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

    PubMed

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

    2015-03-01

    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. PMID:25791542

  17. Deletion of tumor progression locus 2 attenuates alcohol-induced hepatic inflammation

    PubMed Central

    Stice, Camilla P.; Hussain, Sajid; Liu, Chun; Ausman, Lynne M.

    2016-01-01

    Background The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine-threonine kinase that functions as a critical regulator of inflammatory pathways by up-regulating production of inflammatory cytokines. The present study aims to fill the gap in knowledge regarding the involvement of TPL2 in the mechanism of alcohol-induced hepatic inflammation. Methods Male TPL2−/− knockout (TPL2KO) mice and TPL2+/+ wild-type (WT) mice were group pair-fed with Lieber-DeCarli liquid ethanol diet (EtOH diet, 27% energy from EtOH) or control diet (ctrl diet) for 4 weeks. Both histological and molecular biomarkers involved in the induction of hepatic inflammation by alcohol consumption were examined. Results Consumption of the EtOH diet in WT mice lead to a significant induction of TPL2 mRNA expression as compared with WT mice fed ctrl diet. A significant induction in inflammatory foci and steatosis was also observed in WT mice fed EtOH diet. The deletion of TPL2 significantly reduced inflammatory foci in the liver of mice consuming both ctrl and EtOH diets as compared to their respective WT controls. This reduction was associated with suppression of hepatic inflammatory gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) and macrophage marker F4/80. In addition, histological analysis of livers revealed that TPL2 deletion resulted in reduced steatosis in both ctrl (significant) and EtOH (non-significant) diet-fed mice as compared to their respective WT controls. Conclusions The demonstration that TPL2 deletion attenuates alcohol-induced hepatic inflammation provides evidence of a novel role for TPL2 in the pathogenesis of ALD. PMID:26904554

  18. Blood alcohol concentration and self-reported alcohol ingestion in acute poisoned patients who visited an emergency department

    PubMed Central

    2013-01-01

    Background Many acute poisoned patients have co-ingested alcohol in the emergency department (ED). This study aimed to estimate the blood alcohol concentration (BAC) of acute poisoned patients who visited an ED by age and gender distribution and to determine whether it is possible to obtain self-reports of alcohol ingestion among poisoned patients. Method A retrospective medical chart review was conducted for all patients who visited the ED with acute poisoning between January 2004 and February 2008. Data regarding the patients age, gender, BAC, self-reported alcohol ingestion, poison ingested, time elapsed since poison exposure, presence of suicide attempts, and self-reported alcohol ingestion were collected. Patients were classified into two groups based on serum alcohol levels (?10mg/dl, >10mg/dl). Results Of the 255 subjects, 88 subjects (34.5%) were included in the non-alcohol group and 167 subjects (65.5%) were included in the alcohol group. 227 subjects (89.0%) showed suicide intention. Using the 201 subjects who completed the self-report of alcohol ingestion, self-report resulted in 96.6% sensitivity and 86.7% specificity for the assessment of alcohol ingestion. The positive and negative predictive values for self-report were 91.2% and 94.7%, respectively. The median (interquartile range) BAC of the 97 males in the sample was 85.0 (10.0-173.5) mg/dl, and that of the 158 females was 32.0 (4.0-137.5) mg/dl (p?=?0.010). The distribution of age in the groups was significantly different between the alcohol and non-alcohol groups (p?=?0.035), and there was a significant difference in the mean BAC with respect to age for males (p?=?0.003). Conclusion This study showed that over two-thirds of patients presenting with acute poisoning had a BAC?>?10mg/dl. Most of patients visited by suicide attempt. Males had a higher BAC than did females. Self-reported alcohol ingestion in acute poisoned patients showed high sensitivity and specificity. PMID:23574916

  19. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    SciTech Connect

    Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup -}) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH{sup -} and hepatic ADH-normal (ADH{sup +}) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was {approx} 1.5-fold greater in ADH{sup -} vs. ADH{sup +} deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH{sup -} deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  20. Acute hepatitis induced by a Chinese herbal product Qibao Meiran Wan: a case study

    PubMed Central

    Li, Xiaoyan; Qu, Caihong; He, Qiong; Chen, Wenying; Zhang, Xiaojuan; Liu, Xiaoqi; Liu, Yuxing; Tang, Yongbo

    2015-01-01

    Qibao Meiran Wan is a Chinese herbal product sold as a therapy for tonifying the liver and kidney, dizziness, premature graying of hair, backache, constipation, and night sweats. It is widely available in Chinese pharmacies and drugstores and is sold without prescription. We describe a case of acute liver injury in a 26-year-old Chinese man who developed symptomatic hepatitis 1 month after starting Qibao Meiran Wan. There was no evidence of viral hepatitis, Epstein-Barr virus, cytomegalovirus, autoimmune hepatitis, or Budd-Chiari syndrome. The liver injury slowly resolved over 20 days after discontinuing the herbal product. Herbal toxicity was later confirmed by a liver biopsy. Qibao Meiran Wan contains a mixture of several plants including Polygonum multiflorum, which was previously associated with hepatotoxicity. To our knowledge, this is the first report of hepatotoxicity by Qibao Meiran Wan. Clinicians treating patients with acute hepatitis of unclear etiology should pay attention to the consumption of Qibao Meiran Wan. PMID:26379995

  1. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice.

    PubMed

    Kumar, Sudhir; Wang, Jiang; Rani, Richa; Gandhi, Chandrashekhar R

    2016-01-01

    Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8-10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID:26808690

  2. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice

    PubMed Central

    Kumar, Sudhir; Wang, Jiang; Rani, Richa; Gandhi, Chandrashekhar R.

    2016-01-01

    Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8–10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID:26808690

  3. Diet and alcohol effects on the manifestation of hepatic porphyrias.

    PubMed

    Cripps, D J

    1987-04-01

    Porphyria cutanea tarda (PCT) is the most frequently reported type of porphyria. The average patient is male more than 40 years old with a history of alcohol consumption. In women the incidence of PCT has increased with use of estrogens for birth control. The cutaneous features are those of chronic porphyrin photosensitivity on the light-exposed area of the skin: pigmentation, hirsuitism and fragility, and vesiculobullae, which has prompted the expression bullosa actinica et mechanica. One-third of the patients have glucose intolerance. PCT has been reported frequently among the Bantu people in South Africa as resulting from combinations of alcohol and cooking in ironware. The average patient has a higher than normal hematocrit, which is used as a guide to treatment by phlebotomy ranging from 8 to 14 units removed every 2-4 wk. Chemically induced PCT has been reported with chlorinated hydrocarbons, the best-known of which is hexachlorobenzene (HCB). Porphyria was noted in more than 3,000 patients in southeast Turkey between 1955 and 1961, because of consumption of seed wheat treated with HCB. In addition, more than 1,000 children under the age of 1 year died because HCB was transferred from the mother, either via the placenta or through breast milk. PMID:3556614

  4. Acute hepatitis C infection in a renal transplant recipient: primacy of the liver or kidney?

    PubMed

    Althaf, Mohammed Mahdi; Abdelsalam, Mohamed Said; Rashwan, Mohamed; Nadri, Quaid

    2014-01-01

    We present a case where a renal transplant recipient contracted chronic hepatitis C virus (HCV) infection post-transplantation. The disease progressed and deteriorated leading to fibrosing cholestatic hepatitis that mandated treatment. Treatment with pegylated interferon α-2a and ribavirin was successful in salvaging the liver and eradicating the virus but as a consequence lead to treatment-resistant acute rejection and loss of the renal allograft. PMID:24907214

  5. Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations.

    PubMed

    Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert

    2014-04-01

    The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behavior. We have shown significant population-dependent alcohol-induced changes in zebrafish behavior and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2 × 3 (chronic × acute) between-subject alcohol exposure paradigm randomized for two zebrafish populations, AB and SF. Each fish first received the particular chronic treatment (0 or 0.5 vol/vol% alcohol) and subsequently the acute exposure (0, 0.5 or 1.0% alcohol). We report changes in levels of dopamine, DOPAC, serotonin, 5HIAA, glutamate, GABA, aspartate, glycine and taurine as quantified from whole brain extracts using HPLC. We also analyze monoamine oxidase and tyrosine hydroxylase enzymatic activity. The results demonstrate that compared to SF, AB is more responsive to both acute alcohol exposure and acute alcohol withdrawal at the level of neurochemistry, a finding that correlates well with prior behavioral observations and one which suggests the involvement of genes in the observed alcohol effects. We discuss correlations between the current results and prior behavioral findings, and stress the importance of characterization of zebrafish strains for future behavior genetic and psychopharmacology studies. PMID:24381007

  6. Acute and Chronic Alcohol Administration: Effects on Performance of Zebrafish in a Latent Learning Task

    PubMed Central

    Luchiari, Ana C; Salajan, Diana C; Gerlai, Robert

    2015-01-01

    Alcohol abuse is a major medical problem. Zebrafish have been proposed to model alcohol related human disorders. Alcohol impairs learning and memory. Here, we analyze the effects of alcohol on performance of zebrafish in a recently developed latent learning paradigm. We employ a 2 × 3 × 2 experimental design (chronic × acute alcohol treatment × path blocked). The latent learning task had two phases: one, 30 min long exploration trials (16 days, 1 trial/day) with left or right path of a complex maze blocked, and two, a subsequent probe trial with all paths open leading to a goal box that now contained stimulus fish. During the 16 days each fish received one of two chronic treatments: freshwater or 0.50% (vol/vol%) alcohol. Subsequently, fish were immersed for 1h in one of the following solutions: 0.00 (freshwater), 0.50 or 1.00% alcohol, the acute challange. Behavior of fish was recorded during the probe trial that commenced immediately after the acute treatment. Path choices, latency to leave the start box and to enter the goal box, time spent in the goal box, distance travelled, and duration of freezing were quantified. We found that acute exposure to 1.00% alcohol after chronic freshwater disrupted learning performance, so did exposure to freshwater after chronic alcohol treatment (withdrawal). We also found exposure to chronic alcohol to diminish the effect of subsequent acute alcohol suggesting development of tolerance. Our results demonstrate that analysis of learning performance of zebrafish allows detection of alcohol-induced functional changes. The simplicity and scalability of the employed task also imply the utility of the zebrafish in high throughput drug screens. PMID:25557800

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

    PubMed Central

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

    2016-01-01

    Purpose 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. Materials and Methods 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. Results 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. Conclusion 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. PMID:26996565

  8. Acute and chronic effect of ethanol on hepatic albumin synthesis in rat liver in vitro

    SciTech Connect

    Ohtake, H.; Kato, S.; Murawaki, Y.; Kishimoto, Y.; Wakushima, T.; Hirayama, C.

    1986-08-01

    To study the effects of ethanol and its metabolite on albumin metabolism, we examined the hepatic albumin synthesis and secretion in male Wistar rats in vitro, following acute and chronic ethanol administration. After acute ethanol administration, proalbumin synthesis in rat liver in vitro, declined to 47% of the control level at 4 hrs, the lowest level, and increased thereafter to slightly higher than the control level at 16 hrs. On the other hand, chronic ethanol administration for 4 weeks, increased proalbumin synthesis to 1.5 times that of the control level. In the acute ethanol group, a significant negative correlation was observed between proalbumin radioactivity and the concentration of hepatic ethanol and acetaldehyde. The variation between proalbumin radioactivity and hepatic ethanol concentration was wider than the variation between proalbumin and hepatic acetaldehyde. In the chronic ethanol group, ethanol was not detected in the liver. No significant differences from the proalbumin/albumin ratio were seen at any time point after acute or chronic ethanol administration. These findings suggest that the effects of ethanol on hepatic albumin synthesis differ with the method of ethanol administration, and acetaldehyde and/or ethanol is involved in the reduction in albumin synthesis, however, proalbumin-albumin conversion is not disturbed.

  9. Acute Hepatic Necrosis Caused by Salmonella enterica Serotype I 4,5,12:−:1,2 in a Dog

    PubMed Central

    Meiring, Thelma; Grant, Andrew J.; Watson, Penny J.

    2015-01-01

    Acute hepatic necrosis was diagnosed in a dog. Gram staining and fluorescence in situ hybridization identified Salmonella enterica in the liver, subsequently confirmed as S. enterica serotype I 4,5,12:−:1,2. This is the first report of acute hepatic necrosis with liver failure caused by Salmonella in a dog. PMID:26292301

  10. Hepatic thyroid hormone levels following chronic alcohol consumption: direct experimental evidence in rats against the existence of a hyperthyroid hepatic state.

    PubMed

    Teschke, R; Moreno, F; Heinen, E; Herrmann, J; Krüskemper, H L; Strohmeyer, G

    1983-01-01

    To study the effect of chronic alcohol consumption on hepatic levels of thyroid hormones, female Sprague-Dawley rats (n = 24) were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of total calories) or isocaloric carbohydrates for 21 days. Compared to controls, chronic alcohol consumption failed to result in a significant change of hepatic thyroid hormone levels (thyroxine: 14.7 +/- 1.81 ng per gm of liver wet weight vs. 15.0 +/- 1.59; triiodothyronine: 2.60 +/- 0.16 ng per gm of liver wet weight vs. 2.66 +/- 0.18). Similar results were obtained when the hepatic levels of thyroid hormones were expressed per total liver, per gram of liver protein or per 100 gm of body weight. Moreover, prolonged alcohol ingestion led to a significant reduction of serum total thyroxine by 31.6% (p less than 0.001), free thyroxine by 38.9% (p less than 0.02), total triiodothyronine by 40.2% (p less than 0.001) and free triiodothyronine by 56.1% (p less than 0.001) when compared to their pair-fed controls, whereas thyroid-stimulating hormone levels remained virtually unchanged. These data, therefore, clearly show that chronic alcohol consumption is incapable of creating a hyperthyroid hepatic state in rats, and limit the rationale for antithyroid treatment in patients with alcoholic liver disease. PMID:6683240

  11. A Snapshot of the Hepatic Transcriptome: Ad Libitum Alcohol Intake Suppresses Expression of Cholesterol Synthesis Genes in Alcohol-Preferring (P) Rats

    PubMed Central

    Klein, Jonathon D.; Sherrill, Jeremy B.; Morello, Gabriella M.; San Miguel, Phillip J.; Ding, Zhenming; Liangpunsakul, Suthat; Liang, Tiebing; Muir, William M.; Lumeng, Lawrence; Lossie, Amy C.

    2014-01-01

    Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (∼7.43 g ethanol/kg/day) in inbred alcohol-preferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake. PMID:25542004

  12. A snapshot of the hepatic transcriptome: ad libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats.

    PubMed

    Klein, Jonathon D; Sherrill, Jeremy B; Morello, Gabriella M; San Miguel, Phillip J; Ding, Zhenming; Liangpunsakul, Suthat; Liang, Tiebing; Muir, William M; Lumeng, Lawrence; Lossie, Amy C

    2014-01-01

    Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (? 7.43 g ethanol/kg/day) in inbred alcohol-preferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake. PMID:25542004

  13. Transient Receptor Potential Vanilloid 1 Gene Deficiency Ameliorates Hepatic Injury in a Mouse Model of Chronic Binge Alcohol-Induced Alcoholic Liver Disease

    PubMed Central

    Liu, Huilin; Beier, Juliane I.; Arteel, Gavin E.; Ramsden, Christopher E.; Feldstein, Ariel E.; McClain, Craig J.; Kirpich, Irina A.

    2016-01-01

    Experimental alcohol-induced liver injury is exacerbated by a high polyunsaturated fat diet rich in linoleic acid. We postulated that bioactive oxidized linoleic acid metabolites (OXLAMs) play a critical role in the development/progression of alcohol-mediated hepatic inflammation and injury. OXLAMs are endogenous ligands for transient receptor potential vanilloid 1 (TRPV1). Herein, we evaluated the role of signaling through TRPV1 in an experimental animal model of alcoholic liver disease (ALD). Chronic binge alcohol administration increased plasma OXLAM levels, specifically 9- and 13-hydroxy-octadecadienoic acids. This effect was associated with up-regulation of hepatic TRPV1. Exposure of hepatocytes to these OXLAMs in vitro resulted in activation of TRPV1 signal transduction with increased intracellular Ca2+ levels. Genetic depletion of TRPV1 did not blunt hepatic steatosis caused by ethanol, but prevented hepatic injury. TRPV1 deficiency protected from hepatocyte death and prevented the increase in proinflammatory cytokine and chemokine expression, including tumor necrosis factor-α, IL-6, macrophage inflammatory protein-2, and monocyte chemotactic protein 1. TRPV1 depletion markedly blunted ethanol-mediated induction of plasminogen activator inhibitor-1, an important alcohol-induced hepatic inflammation mediator, via fibrin accumulation. This study indicates, for the first time, that TRPV1 receptor pathway may be involved in hepatic inflammatory response in an experimental animal model of ALD. TRPV1-OXLAM interactions appear to play a significant role in hepatic inflammation/injury, further supporting an important role for dietary lipids in ALD. PMID:25447051

  14. Acute hepatitis C virus infection assessment among chronic hemodialysis patients in the Southwest Parana State, Brazil

    PubMed Central

    Engel, Maricea; Malta, Fernanda M; Gomes, Michele MS; Mello, Isabel MVGC; Pinho, João RR; Ono-Nita, Suzane K; Carrilho, Flair J

    2007-01-01

    Background Chronic hemodialysis patients are at higher risk for acquiring hepatitis C virus (HCV). The prevalence varies among different countries and hemodialysis centers. Although guidelines for a comprehensive infection control program exist, the nosocomial transmission still accounts for the new cases of infection. The aim of this study was analyze the follow up of newly acquired acute hepatitis C cases, during the period from January 2002 to May 2005, in the Hemodialysis Center, located in the Southwest region of Parana State, Brazil and to analyze the effectiveness of the measures to restrain the appearance of new cases of acute hepatitis C. Methods Patients were analyzed monthly with anti-HCV tests and ALT measurements. Patients with ALT elevations were monitored for possible acute hepatitis C. Results During this period, 32 new cases were identified with acute hepatitis C virus infection. Blood screening showed variable ALT levels preceding the anti-HCV seroconversion. HCV RNA viremia by PCR analysis was intermittently and even negative in some cases. Ten out of 32 patients received 1 mcg/kg dose of pegylated interferon alfa-2b treatment for 24 weeks. All dialysis personnel were re-trained to strictly follow the regulations and recommendations regarding infection control, proper methods to clean and disinfect equipment were reviewed and HCV-positive patients were isolated. Conclusion Laboratory tests results showed variable ALT preceding anti-HCV seroconversion and intermittent viremia. The applied recommendations contributed importantly to restrain the appearance of new cases of acute hepatitis C in this center and the last case was diagnosed in May 2004. PMID:17408470

  15. Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation.

    PubMed

    Arai, Y; Kanda, J; Nakasone, H; Kondo, T; Uchida, N; Fukuda, T; Ohashi, K; Kaida, K; Iwato, K; Eto, T; Kanda, Y; Nakamae, H; Nagamura-Inoue, T; Morishima, Y; Hirokawa, M; Atsuta, Y; Murata, M

    2016-01-01

    Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients. PMID:26367230

  16. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  17. Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication

    PubMed Central

    Souza-Smith, Flavia M.; Kurtz, Kristine M.; Molina, Patricia E.; Breslin, Jerome W.

    2010-01-01

    Objective Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to concious, unrestrained rats through surgically-implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results Lymphatics isolated from alcohol-intoxicated animals displayed slgnificantly decreased contraction frequency (CF) than the dextrose group, elevated stroke volume index (SVI) versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. PMID:21040117

  18. Does acute alcohol intoxication cause transaminase elevations in children and adolescents?

    PubMed

    Binder, Christoph; Knibbe, Karoline; Kreissl, Alexandra; Repa, Andreas; Thanhaeuser, Margarita; Greber-Platzer, Susanne; Berger, Angelika; Jilma, Bernd; Haiden, Nadja

    2016-03-01

    Several long-term effects of alcohol abuse in children and adolescents are well described. Alcohol abuse has severe effects on neurodevelopmental outcome, such as learning disabilities, memory deficits, and decreased cognitive performance. Additionally, chronic alcohol intake is associated with chronic liver disease. However, the effects of acute alcohol intoxication on liver function in children and adolescents are not well characterized. The aim of this study was to determine if a single event of acute alcohol intoxication has short-term effects on liver function and metabolism. All children and adolescents admitted to the Department of Pediatrics and Adolescent Medicine between 2004 and 2011 with the diagnosis "acute alcohol intoxication" were included in this retrospective analysis. Clinical records were evaluated for age, gender, alcohol consumption, blood alcohol concentration, symptoms, and therapy. Blood values of the liver parameters, CK, creatinine, LDH, AP, and the values of the blood gas analysis were analyzed. During the 8-year study period, 249 children and adolescents with the diagnosis "acute alcohol intoxication" were admitted, 132 (53%) girls and 117 (47%) boys. The mean age was 15.3 ± 1.2 years and the mean blood alcohol concentration was 0.201 ± 0.049%. Girls consumed significantly less alcohol than boys (64 g vs. 90 g), but reached the same blood alcohol concentration (girls: 0.199 ± 0.049%; boys: 0.204 ± 0.049%). The mean values of liver parameters were in normal ranges, but AST was increased in 9.1%, ALT in 3.9%, and γGT in 1.4%. In contrast, the mean value of AST/ALT ratio was increased and the ratio was elevated in 92.6% of all patients. Data of the present study showed significant differences in the AST/ALT ratio (p < 0.01) in comparison to a control group. Data of the present study indicate that there might be an effect of acute alcohol intoxication on transaminase levels. The AST/ALT ratio seems to reflect the damage in hepatocytes after intensive alcohol consumption. The present study indicates a sex-specific difference in alcohol metabolism and effects between girls and boys: girls need less alcohol than boys to achieve the same blood alcohol levels than boys, and are more prone to loss of consciousness. PMID:26992701

  19. Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1{alpha} in rats

    SciTech Connect

    Lieber, Charles S. Leo, Maria A.; Wang Xiaolei; DeCarli, Leonore M.

    2008-05-23

    The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-{gamma} coactivator1{alpha} (PGC-1{alpha}) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1{alpha} mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1{alpha}, while the transcription factor PPAR-{gamma} remained unchanged. However, when the lipid composition of the alcohol diet was changed by replacing long-chain triglycerides (LCT) with medium chain triglycerides (MCT), SIRT1 and PGC-1{alpha} mRNA were restored to near control levels. This study demonstrates that alcohol reduces key energy sensing proteins and that replacement of LCT by MCT affects the transcription of these genes. Since there is a pathophysiological link between SIRT1 and PGC-1{alpha} and mitochondrial energy, the implication of the study is that mitochondrial dysfunction due to alcohol abuse can be treated by dietary modifications.

  20. Regulation of FOXO3 by phosphorylation and methylation in Hepatitis C virus infection and alcohol exposure

    PubMed Central

    Tikhanovich, Irina; Kuravi, Sudhakiranmayi; Campbell, Roosevelt V.; Kharbanda, Kusum; Artigues, Antonio; Villar, Maria T.; Weinman, Steven A.

    2013-01-01

    Hepatitis C infection produces chronic liver injury that is significantly exacerbated by alcohol consumption. While multiple mechanisms contribute to this synergy, a viral-induced loss of antioxidant responses has been shown to play an important role. This study examined the effects of HCV infection and alcohol on the regulation of the transcription factor FOXO3, an important regulator of SOD2 expression, a tumor suppressor, and a component of the hepatic antioxidant response system. FOXO3 was activated by either HCV or alcohol alone but suppressed by the combination. To understand this paradoxical result, we applied a capillary isoelectric focusing (IEF) method to determine the pattern of FOXO3 post-translational modifications (PTMs) induced by HCV and alcohol. We observed the presence of multiple different nuclear and cytosolic species of FOXO3 and used anti phosphoserine, acetyl-lysine, methylarginine and ubiquitin antibodies to identify the PTM patterns present in each species. HCV caused multiple changes including phosphorylation of FOXO3 at S-574, a novel JNK site, which promoted nuclear translocation and transcription. Ethanol suppressed arginine-methylation of FOXO3 promoting nuclear export and degradation of the JNK phosphorylated form. Human liver biopsy samples showed the presence of the HCV-specific form of FOXO3 in HCV-infected livers but not in normal liver or nonalcoholic steatohepatitis. Conclusion The development of this novel IEF method for the simultaneous quantification of differently modified FOXO3 species allowed us to demonstrate how HCV and alcohol combine to modify a complex pattern of FOXO3 PTMs that contribute to pathogenesis. This approach will allow further dissection of the role of protein PTMs in viral liver disease. PMID:23857333

  1. [Incidence of posthepatic sequelae of acute viral hepatitis C].

    PubMed

    Reinhardt, M; Jorke, D; Krombholz, B; Jahn, G; Haufe, C

    1983-05-01

    There are not yet any ascertained results concerning the prognosis of the non-A/non-B hepatitis not depending on transfusion. In an identical source of infection meanwhile several working teams in the GDR by means of long-term observations for three years control groups of women able to propagate who were incubated by a hepatitis C-virus (of the non-A/non-B group of the hepatotropic viruses), so that first evidence on posthepatitic sequelae after hepatitis C is possible. Of 115 women who were treated with anti-D-globulin contaminated with C virus 57 women fell ill (= 49.5%). Of them 39 patients (3 68.4%) were cured after 3 years, 7 patients (6 12.3%) showed the signs of a residual hepatitis, 10 patients (3 17.5%) showed a chronically persisting and 1 patient (= 1.75%) a chronically active hepatitis. The results presented are compared to those of other working teams of our country. PMID:6410600

  2. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat

    PubMed Central

    Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

    2010-01-01

    BACKGROUND Alcohol withdrawal, refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with N/OFQ significantly reduces alcohol consumption and attenuates alcohol-seeking behaviour induced by environmental conditioning factors or by stress in rats. In the present study we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. METHODS For this purpose animals were subjected to a 6 day chronic alcohol intoxication (by intragastric administration) and at 8, 10 and 12 hours following cessation of alcohol exposure they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0 and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety another group of rats was subjected to ethanol intoxication and after one week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12-h later were tested in the EPM following ICV N/OFQ (0.0, 1.0 and 2.0μg/rat). RESULTS Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. CONCLUSIONS The present findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. PMID:21223310

  3. Pharmacokinetics and metabolism of digoxin- and beta-methyl-digoxin-12aplha-3 H in patients with acute hepatitis.

    PubMed

    Zilly, W; Richter, E; Rietbrock, N

    1975-03-01

    Pharmocokinetics and metabolism of digoxin and beta-methyldigoxin have been studied in patients with acute hepatits after intravenous administration of both H-labeled glycosides. In contrast to digoxin, the rate of decline of radioactivity after administration of beta-methyldigoxin was significantly retarded in patients with acute hepatitis. The increase in plasma concentration after beta-methyldigoxin to patients with acute hepatitis is probably related to decreased demethylation. PMID:1120395

  4. Influence of acid-secretion blockers on gastric and hepatic alcohol dehydrogenase in rat.

    PubMed

    Pozzato, G; Stebel, M; Lunazzi, G; Moretti, M; Franzin, F

    1992-11-01

    The effects of Cimetidine, Ranitidine, and Omeprazole on gastric and hepatic alcohol-dehydrogenase (ADH) activity was studied in rat. Two apparent values for Km were found for gastric ADH (220 mmol l-1 and 1043 mmol l-1 respectively) and one for hepatic ADH (0.54 mmol l-1). Cimetidine was shown to exert an uncompetitive inhibition of low Km gastric ADH with a Ki of 0.167 mmol l-1 and a competitive inhibition of high Km gastric ADH with a Ki 2.3 mmol l-1. Ranitidine was found to present non-competitive inhibition only on low Km gastric ADH with a Ki of 12 mmol l-1. Omeprazole affects only low Km gastric ADH with a Ki of 5.6 mmol l-1 and presents a linear-mixed type of inhibition. Hepatic ADH was shown to be competitively inhibited only by Cimetidine with a Ki of 6.0 mmol l-1 whereas no inhibition for either Ranitidine and Omeprazole was observed. These results confirm the inhibitory action of Cimetidine on both gastric and hepatic ADH; Ranitidine and Omeprazole show minor effects on ADHS activity and probably on first-pass metabolism. PMID:1455167

  5. Early activated hepatic stellate cell-derived molecules reverse acute hepatic injury

    PubMed Central

    Chang, Wen-Ju; Song, Lu-Jun; Yi, Tuo; Shen, Kun-Tang; Wang, Hong-Shan; Gao, Xiao-Dong; Li, Min; Xu, Jian-Min; Niu, Wei-Xin; Qin, Xin-Yu

    2015-01-01

    AIM: To test whether hepatic stellate cells (HSCs) at different activation stages play different roles in acetaminophen (APAP)-induced acute liver injury (ALI). METHODS: HSCs were isolated from mouse liver and cultured in vitro. Morphological changes of initiation HSCs [HSCs (5d)] and perpetuation HSCs [HSCs (p3)] were observed by immunofluorescence and transmission electron microscopy. The protective effects of HSC-derived molecules, cell lysates and HSC-conditioned medium (HSC-CM) were tested in vivo by survival and histopathological analyses. Liver injury was determined by measuring aminotransferase levels in the serum and by histologic examination of tissue sections under a light microscope. Additionally, to determine the molecular mediators of the observed protective effects of initiation HSCs, we examined HSC-CM using a high-density protein array. RESULTS: HSCs (5d) and HSCs (p3) had different morphological and phenotypic traits. HSCs (5d) presented a star-shaped appearance with expressing α-SMA at non-uniform levels between cells. However, HSCs (p3) evolved into myofibroblast-like cells without lipid droplets and expressed a uniform and higher level of α-SMA. HSC-CM (5d), but not HSC-CM (p3), provided a significant survival benefit and showed a dramatic reduction of hepatocellular necrosis and panlobular leukocyte infiltrates in mice exposed to APAP. However, this protective effect was abrogated at higher cell masses, indicating a therapeutic window of effectiveness. Furthermore, the protein array screen revealed that HSC-CM (5d) was composed of many chemokines and growth factors that correlated with inflammatory inhibition and therapeutic activity. When compared with HSC-CM (p3), higher levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1γ, hepatocyte growth factor, interleukin-10, and matrix metalloproteinase-2, but lower levels of stem cell factor and Fas-Ligand were observed in HSC-CM (5d). CONCLUSION: These data indicated that initiation HSCs and perpetuation HSCs were different in morphology and protein expression, and provided the first experimental evidence of the potential medical value of initiation HSC-derived molecules in the treatment of ALI. PMID:25892868

  6. HEPATIC AND RENAL ASSESSMENT OF ACUTE EXPOSURE TO INHALED EPICHLOROHYDRIN: TOXICOLOGICAL EVALUATION AND EXPOSURE MODELING

    EPA Science Inventory

    To determine the hepatic and enal effects of acute exposure to inhaled epichlorohydrin (ECH), male F-344 rats were exposed either to 0 or to 100 ppm ECH by inhalation for 4 hours. epatic and renal toxicity-were assessed at the termination of exposure and on the first, second and ...

  7. Use of iron colloid-enhanced MRI for study of acute radiation-induced hepatic injury

    SciTech Connect

    Suto, Yuji; Ametani, Masaki; Kato, Takashi; Hashimoto, Masayuki; Kamba, Masayuki; Sugihara, Syuji; Ohta, Yoshio

    1996-03-01

    We present a case with acute radiation-induced hepatic injury using chondroitin sulfate iron colloid (CSIC)-enhanced MRI. Uptake of CSIC was decreased in the irradiated portion of the liver. CSIC-enhanced MRI is useful for obtaining information on the function of the reticuloendothelial system and demarcates between irradiated and nonirradiated zones. 18 refs., 3 figs

  8. A case of heart failure due to alcoholic cardiomyopathy combined with acute pulmonary embolism

    PubMed Central

    Xiao, Feng; Yuan, Wei; Li, Xiaorong; Wang, Gannan; Jiang, Ting; Wang, Weiwei; Zhang, Jinsong; Li, Ping; Qi, Lianwen

    2014-01-01

    It has not been reported that cases of alcoholic cardiomyopathy (ACM) combined with acute pulmonary embolism (PE). We hereby present a case of a 48-year-old male with ACM with significant enlargement of the heart and heart failure is described. Then, the patient was seized with acute PE which was confirmed by specific examination and his symptoms. PMID:25276392

  9. Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus

    PubMed Central

    Cha, Jae Hwang; Ra, Sang Ho; Park, Yu Mi; Ji, Yong Kwan; Lee, Ji Hyun; Park, So Yeon; Baik, Soon Koo; Kwon, Sang Ok; Cho, Mee Yon

    2013-01-01

    Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review. PMID:24459648

  10. Aberrant Hepatic Methionine Metabolism and Gene Methylation in the Pathogenesis and Treatment of Alcoholic Steatohepatitis

    PubMed Central

    Halsted, Charles H.; Medici, Valentina

    2012-01-01

    The pathogenesis of alcoholic steatohepatitis (ASH) involves ethanol-induced aberrations in hepatic methionine metabolism that decrease levels of S-adenosylmethionine (SAM), a compound which regulates the synthesis of the antioxidant glutathione and is the principal methyl donor in the epigenetic regulation of genes relevant to liver injury. The present paper describes the effects of ethanol on the hepatic methionine cycle, followed by evidence for the central role of reduced SAM in the pathogenesis of ASH according to clinical data and experiments in ethanol-fed animals and in cell models. The efficacy of supplemental SAM in the prevention of ASH in animal models and in the clinical treatment of ASH will be discussed. PMID:22007317

  11. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers.

    PubMed

    Sanna, Claudia; Rosso, Chiara; Marietti, Milena; Bugianesi, Elisabetta

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas) and extra-intestinal sites (kidney in men, and breast in women). Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC), but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites. PMID:27187365

  12. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

    PubMed Central

    Sanna, Claudia; Rosso, Chiara; Marietti, Milena; Bugianesi, Elisabetta

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas) and extra-intestinal sites (kidney in men, and breast in women). Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC), but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites. PMID:27187365

  13. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice

    PubMed Central

    Rodríguez, Amaia; Moreno, Natalia R.; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M.; Frühbeck, Gema

    2015-01-01

    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity. PMID:26159457

  14. High prevalence of hantavirus infection in a group of Chinese patients with acute hepatitis of unknown aetiology.

    PubMed

    Meng, G; Lan, Y; Nakagawa, M; Maehara, T; Mitani, K; Tomiyama, T; Che, X G; Ohkubo, A

    1997-07-01

    In southwestern China, small but substantial numbers of patients with acute hepatitis were found without known hepatropic viral infections (hepatitis A, B, C, D or E, cytomegalovirus, Epstein-Barr virus) and were receiving no hepatotoxic drugs. Prevalence of antibodies, both neutralizing and specific immunoglobulin (Ig)M and IgG, to Hantaan virus were evaluated in a cohort of 136 such patients: 83 were of unknown aetiology, 53 had known viral hepatitis and 59 healthy subjects acted as controls. The results showed that the incidence of neutralizing antibody to Hantaan virus in acute hepatitis patients with non-hepatitis A-E virus infections (13 of 83) was significantly higher than in those with A-E infections (0 of 53, P<0.01). Furthermore, the incidence of specific IgM antibody to Hantaan virus in acute hepatitis patients with non-hepatitis A-E virus infections (6 of 83) was significantly higher than in those with A-E infections (0 of 53, P<0.05) and in healthy subjects (0 of 59, P < 0.05). These findings suggest that Hantaan virus may be an important agent, contributing, at least in southwestern China, to a significant number of the cases of acute hepatitis of unknown aetiology. This hantavirus infection resulted in an acute hepatitis, differing from the typical diseases: haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). PMID:9278220

  15. Cimetidine prevents alcoholic hepatic injury in the intragastric feeding rat model.

    PubMed

    Nanji, A A; Zhao, S; Khwaja, S; Sadrzadeh, S M; Waxman, D J

    1994-05-01

    Cytochrome P450 induction is believed to be important in the pathogenesis of alcoholic hepatic disease. Because cimetidine is a general inhibitor of cytochrome P450 enzymes, it was hypothesized that it could be useful in preventing alcoholic hepatic injury. An intragastric feeding model was used these studies. Experimental animals were divided into groups of four to five rats/group and fed the following diets: corn oil+dextrose, corn oil+ethanol (CE) and corn oil+ethanol+cimetidine (250 mg kg-1 day-1) (CEC). The rats in each group were sacrificed at the following time intervals: 2 weeks, 1 month and 2 months. For each animal, the severity of the pathologic findings and relative protein levels of cytochromes P450 2E1, 2B and 4A were measured. In addition, plasma levels of thromboxane B2, 6-ketoprostaglandin F1 alpha and 8-isoprostane were also measured. The most significant finding was that cimetidine completely prevented alcoholic hepatic injury in this model system. The pathologic scores (an indication of the severity of injury) were significantly lower in the CEC groups compared with the CE group. There was however, no significant difference in cytochrome P450 2E1, 2B or 4A protein levels between CE and CEC groups. Thromboxane B2 and 8-isoprostane levels were significantly lower and 6-ketoprostaglandin F1 alpha, significantly higher in the CEC group than in the CE group. These results indicate that possible mechanisms involved in the protective action of cimetidine include inhibition of thromboxane production and lipid peroxidation. PMID:8182552

  16. Hepatitis

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Hepatitis KidsHealth > For Teens > Hepatitis Print A A A ... to a liver condition called hepatitis . What Is Hepatitis? The liver is one of the body's powerhouses. ...

  17. Hepatitis

    MedlinePlus

    ... Sledding, Skiing, Snowboarding, Skating Crushes What's a Booger? Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  18. [Fever of unknown origin with granulomatous hepatitis, uveitis and acute renal failure].

    PubMed

    Moret, Ch; Meier, P; Rotman, S; Lepori, M; Lamy, O

    2005-01-12

    A 46-year-old man was referred to our hospital because of fever of unknown origin (FUO). Two months before admission, he noted fever, weight loss, and asthenia. Physical examination revealed only mechanical pains of the right shoulder. In the past, patient's father had a tuberculosis. At the age of 29 years, Brucella granulomatous hepatitis and B hepatitis were diagnosed. The past three years, he developed two episodes of uveitis which resolved with local treatment. The hepatic biopsy revealed only a non specific granulomatous hepatitis. Few days after admission, the patient developed acute renal failure without proteinuria or hematuria. The renal biopsy confirmed the presence of noncaseating granulomas. In the context of the patient, we diagnosed a sarcoidosis. All the symptoms resolved with the initiation of prednisone treatment. The FUO differential diagnosis, and the different aspects of renal sarcoidosis are discussed. PMID:15697147

  19. RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.

    PubMed

    Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D; New, Maria I; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J

    2014-05-27

    The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias. PMID:24821812

  20. RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice

    PubMed Central

    Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D.; New, Maria I.; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J.

    2014-01-01

    The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias. PMID:24821812

  1. μ‐Opioid receptor activation prevents acute hepatic inflammation and cell death

    PubMed Central

    Chakass, Dania; Philippe, David; Erdual, Edmone; Dharancy, Sébastien; Malapel, Mathilde; Dubuquoy, Caroline; Thuru, Xavier; Gay, Jerome; Gaveriaux‐Ruff, Claire; Dubus, Pierre; Mathurin, Philippe; Kieffer, Brigitte L; Desreumaux, Pierre; Chamaillard, Mathias

    2007-01-01

    Background and aims The detrimental impact of opioid agonist on the clinical management of inflammatory diseases remains elusive. Given the anti‐inflammatory properties of the μ‐opioid receptor (MOR) agonists at the intestinal barrier, we hypothesised that MOR activation might also dampen acute hepatic inflammation and cell death—major determinants in the pathogenesis of liver diseases. Patients and methods The expression of MOR in liver biopsy specimens and peripheral blood mononuclear cells of untreated patients with chronic hepatitis C virus infection and controls, primary hepatocytes and cell lines was determined by quantitative PCR, immunoblotting and/or immunohistochemistry. The effects of peripheral MOR agonist (D‐Ala2,NMe‐Phe4,Gly5‐ol (DAMGO)) and/or antagonist (naloxone methiodide) were explored in two models of acute hepatitis in mice. MOR‐deficient mice were used to evaluate the essential regulatory role of MOR during carbon tetrachloride (CCl4)‐induced hepatitis. The role of DAMGO in cell death was investigated using terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL) analysis and quantification of lactate dehydrogenase release. Results The key role of MOR in the prevention of acute hepatic inflammation and cell death in vivo and in vitro is reported. Whereas MOR gene expression increased transiently in the model of acute liver injury and TNFα‐treated HepG2 cells, an impaired expression of MOR mRNA in human chronic hepatitis C samples was found. Furthermore, preventive administration of the selective MOR agonist DAMGO enhanced hepatoprotective‐signalling pathways in vivo that were blocked by using naloxone methiodide. Consistently, genetic and pharmacological inhibition of MOR enhanced the severity associated with experimental hepatotoxin‐induced hepatitis. Finally, treatment with DAMGO was shown to prevent cell death in vitro in HepG2 cells in a MOR‐dependent manner and to prevent concanavalin A‐ and CCl4‐induced cell death in vivo, providing a possible explanation for the anti‐inflammatory role of MOR activation in the liver. Conclusions The results indicate that MOR agonists may prevent acute hepatitis and hold promising therapeutic use to maintain remission in both chronic inflammatory bowel and liver diseases. PMID:17299060

  2. Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

    PubMed Central

    Rogée, Sophie; Le Gall, Morgane; Chafey, Philippe; Bouquet, Jérôme; Cordonnier, Nathalie; Frederici, Christian

    2014-01-01

    ABSTRACT Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In industrialized countries, HEV is considered an emerging zoonotic disease, with swine being the principal reservoir for human contamination. The viral and cellular factors involved in the replication and/or pathogenesis of HEV are still not fully known. Here we report that several cellular pathways involved in cholesterol and lipid metabolism or cell survival were modulated during HEV infection in the swine model. Moreover, we observed a difference between the different swine strains, suggesting that HEV's genetic variability could play a role in pathogenesis. We also identified some proteins known to be involved in other viral cycles. Our study provides insight into the mechanisms modulated during HEV infection and constitutes a useful reference for future work on HEV pathogenesis and virulence. PMID:25320303

  3. Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis

    PubMed Central

    Morales-Ibanez, Oriol; Affò, Silvia; Rodrigo-Torres, Daniel; Blaya, Delia; Millán, Cristina; Coll, Mar; Perea, Luis; Odena, Gemma; Knorpp, Thomas; Templin, Markus F; Moreno, Montserrat; Altamirano, José; Miquel, Rosa; Arroyo, Vicente; Ginès, Pere; Caballería, Juan; Sancho-Bru, Pau; Bataller, Ramon

    2015-01-01

    Objective Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. Design Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. Results Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. Conclusions p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis. PMID:25652085

  4. Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice

    PubMed Central

    Lazaro, Raul; Wu, Raymond; Lee, Sunyoung; Zhu, Nian-Ling; Chen, Chia-Lin; French, Samuel W.; Xu, Jun; Machida, Keigo; Tsukamoto, Hidekazu

    2014-01-01

    Alcoholic hepatitis (AH) is a distinct spectrum of alcoholic liver disease (ALD) with intense neutrophilic (PMN) inflammation and high mortality. Although a recent study implicates osteopontin (SPP1) in AH, SPP1 is also shown to have protective effects on experimental ALD. To address this unsettled question, we examined the effects of SPP1 deficiency in male mice given 40% calories derived from ad libitum consumption of the Western diet high in cholesterol and saturated fat (HCFD) and the rest from intragastric feeding (iG) of alcohol diet without or with weekly alcohol binge. Weekly binge in this new hybrid feeding model shifts chronic ASH with macrophage inflammation and perisinusoidal and pericelluar fibrosis to AH in 57% (15/26) of the mice, accompanied by inductions of chemokines (Spp1, Cxcl1, Il-17a), progenitor genes (Cd133, Cd24, Nanog, Epcam), PMN infiltration, and clinical features of AH such as hypoalbuminemia, bilirubinemia, and splenomegaly. SPP1 deficiency does not reduce the AH incidence and inductions of progenitor and fibrogenic genes but rather enhances the Il-17a induction and PMN infiltration in some mice. Further, in the absence of SPP1, chronic ASH mice without weekly binge begin to develop AH. In conclusion, these results suggest SPP1 has a protective rather than causal role for experimental AH reproduced in our model. PMID:25132354

  5. Effect of alcohol on diethylnitrosamine-induced hepatic toxicity: Critical role of ROS, lipid accumulation, and mitochondrial dysfunction.

    PubMed

    Sun, Quangui; Long, Zi; Wu, Hao; Liu, Ying; Wang, Lele; Zhang, Xiaodi; Wang, Xin; Hai, Chunxu

    2015-10-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh in women worldwide. Chronic heavy alcohol consumption is a major risk factor for the development of HCC. However, the mechanism underlying the direct association between alcohol consumption and HCC is far from completely understood. In the present study, we investigated the effect of chronic consumption of alcohol on diethylnitrosamine (DEN)-induced cytotoxicity, which was essential for the malignant transformation. We showed that alcohol deceased survival of mice treated by DEN and promoted DEN-induced toxicity and hepatic injury. In addition, alcohol promoted DEN-induced increase of proinflammatory factors, collagen content and fibrosis-related genes, including collagen1, 3 and 4, TMIP1, TIMP2 and TGFβ1, and compensatory proliferation. Alcohol may increase alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1) expression, enhanced reactive oxygen species (ROS) generation, and resulted in a vicious circle between ROS generation, lipid accumulation, and mitochondrial dysfunction, aggravating liver injury and toxicity in DEN-treated mice. These results demonstrated that the combination of alcohol and carcinogens could aggravate carcinogen-induced cytotoxicity in the early phase of rumourigenesis through ADH and CYP2E1-generated ROS and the resultant cytotoxic process. The present study provided direct experimental evidence for alcohol-promoted toxicity and hepatic injury in carcinogen (DEN)-treated mice. PMID:26198575

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

    PubMed Central

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

    2016-01-01

    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. PMID:27044768

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

    PubMed

    Stoupis, Christoforos; Ludwig, Karin; Inderbitzin, Daniel; Do, Dai-Do; Triller, Juergen

    2007-02-01

    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 hemorrhage 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. PMID:16932877

  8. Contribution of Hepatitis B to Long-Term Outcome Among Patients With Acute Myocardial Infarction

    PubMed Central

    Kuo, Pei-Lun; Lin, Kun-Chang; Tang, Pei-Ling; Cheng, Chin-Chang; Huang, Wei-Chun; Chiang, Cheng-Hung; Lin, Hsiao-Chin; Chuang, Tzu-Jung; Wann, Shue-Ren; Mar, Guang-Yuan; Cheng, Jin-Shiung; Liu, Chun-Peng

    2016-01-01

    Abstract Although a possible association between hepatitis B and cardiovascular disease has been identified, the impact of viral hepatitis B on long-term prognosis after an acute myocardial infarction (AMI) is uncertain. Therefore, the aim of our study was to evaluate the specific impact of viral hepatitis B on survival after a first AMI through a retrospective analysis of data from the Taiwan National Health Insurance Research Database. This was a nationwide, propensity score-matched case–control study of patients admitted to hospitals between January 2000 and December 2012 with a primary diagnosis of a first AMI. Among the 7671 prospective patients, 244 patients with a confirmed diagnosis of viral hepatitis B infection were identified. A propensity score, one-to-one matching technique was used to match 244 controls to the AMI group for analysis. Controls were matched on the following variables: sex, age, hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accidents, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention (PCI). Overall, viral hepatitis B infection did not influence the 12-year survival rate (P = 0.98). However, survival was lower in female patients with viral hepatitis B infection compared to those without (P = 0.03; hazard ratio, 1.79; 95% confidence interval, 1.08–2.94). Inclusion of percutaneous coronary management improved survival, independent of sex, age, or hepatitis B status. Hepatitis B infection might increase the mortality risk of female patients after a first AMI. PCI may improve the long-term survival of patients after a first AMI, regardless of sex, age, and hepatitis B status. PMID:26844504

  9. Static and dynamic prognostic factors for hepatitis-B-related acute-on-chronic liver failure

    PubMed Central

    Ha, Jung Min; Sohn, Won; Cho, Ju Yeon; Pyo, Jeung Hui; Choi, Kyu; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Chul; Paik, Seung Woon; Yoo, Byung Chul

    2015-01-01

    Background/Aims Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. Methods Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. Results A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (≥28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (≥grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). Conclusions Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure. PMID:26523268

  10. Acute Alcohol Drinking Promotes Piecemeal Percepts during Binocular Rivalry.

    PubMed

    Cao, Dingcai; Zhuang, Xiaohua; Kang, Para; Hong, Sang W; King, Andrea C

    2016-01-01

    Binocular rivalry refers to perceptual alternation when two eyes view different images. One of the potential percepts during binocular rivalry is a spatial mosaic of left- and right-eye images, known as piecemeal percepts, which may result from localized rivalries between small regions in the left- and right-eye images. It is known that alcohol increases inhibitory neurotransmission, which may reduce the number of alternations during binocular rivalry. However, it is unclear whether alcohol affects rivalry dynamics in the same manner for both coherent percepts (i.e., percepts of complete left or right images) and piecemeal percepts. To address this question, the present study measured the dynamics of binocular rivalry before and after 15 moderate-to-heavy social drinkers consumed an intoxicating dose of alcohol versus a placebo beverage. Both simple rivalrous stimuli consisting of gratings with different orientations, and complex stimuli consisting of a face or a house were tested to examine alcohol effects on rivalry as a function of stimulus complexity. Results showed that for both simple and complex stimuli, alcohol affects coherent and piecemeal percepts differently. More specifically, alcohol reduced the number of coherent percepts but not the mean dominance duration of coherent percepts. In contrast, for piecemeal percepts, alcohol increased the mean dominance duration but not the number of piecemeal percepts. These results suggested that alcohol drinking may selectively affect the dynamics of transitional period of binocular rivalry by increasing the duration of piecemeal percepts, leading to a reduction in the number of coherent percepts. The differential effect of alcohol on the dynamics of coherent and piecemeal percepts cannot be accounted for by alcohol's effect on a common inhibitory mechanism. Other mechanisms, such as increasing neural noise, are needed to explain alcohol's effect on the dynamics of binocular rivalry. PMID:27092096

  11. Glucocorticoids are ineffective in alcoholic hepatitis: a meta-analysis adjusting for confounding variables.

    PubMed Central

    Christensen, E; Gluud, C

    1995-01-01

    The aim of this study was to perform a meta-analysis of controlled clinical trials of glucocorticoid treatment in clinical alcoholic hepatitis, adjusting for prognostic variables and their possible interaction with therapy, because these trials have given appreciably different results. Weighted logistic regression analysis was applied using the summarised descriptive data (for example, % with encephalopathy, mean bilirubin value) of the treatment and control groups of 12 controlled trials that gave this information. Despite evidence of publication bias favouring glucocorticoid treatment, its overall effect on mortality was not statistically significant (p = 0.20)--the relative risk (steroid/control) was 0.78 (95% confidence intervals 0.51, 1.18). There was indication of interaction between glucocorticoid therapy and gender, but not encephalopathy. Thus, the effect of glucocorticoid treatment may be different (beneficial or harmful) in special patient subgroups. These results do not support the routine use of glucocorticoids in patients with alcoholic hepatitis, including those with encephalopathy. Whether other subgroups may benefit needs further investigation using the individual patient data from the published trials and testing in new randomised trials. PMID:7672658

  12. Protracted impairment of impulse control under an acute dose of alcohol: A time course analysis

    PubMed Central

    Miller, Melissa A.; Fillmore, Mark T.

    2013-01-01

    Alcohol is well-known for impairing impulse control as well as its disruptive effects on other aspects of behavioral functioning, such as motor control. Time-course analyses during a single dose show rapid development of acute tolerance to impairment of motor coordination, reaction time, and levels of subjective intoxication, but no acute tolerance to impairment of the ability to inhibit responses. Evidence for a possible lag in tolerance development to the impairing effects of alcohol on inhibitory control suggests that, as drinkers’ blood alcohol concentration (BAC) declines, they might exhibit prolonged impulsivity despite having an unimpaired ability to initiate action. The present study extended the time-course analysis to examine the recovery of inhibitory control under a dose of alcohol as drinkers’ BAC descended from a peak of 80 mg/100 ml to a zero level. Twenty-four healthy adults were tested following 0.65 g/kg alcohol and a placebo in a counterbalanced order. They performed a cued go/no-go task that measured response inhibition. They also performed tasks that assessed reaction time, motor coordination, and completed ratings of their subjective levels of intoxication. Alcohol initially impaired inhibitory control, response time, and motor coordination and increased subjective ratings of intoxication. However, acute tolerance to the impairing effects of alcohol was observed for measures of response time, motor coordination, and ratings of intoxication and these measures returned to sober (i.e., placebo) levels by the time BAC fell to near zero. By contrast, impairment of inhibitory control showed no acute tolerance and remained impaired even when drinkers’ BAC returned to near zero. Taken together, these results indicate that the disinhibiting effects of alcohol are present even when the impairing effects of alcohol on other aspects of behavior have diminished under the dose. These findings could provide a greater understanding of impulsive behaviors during the descending limb of intoxication. PMID:24286706

  13. Cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine.

    PubMed

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    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. PMID:25999668

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

    PubMed Central

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    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. PMID:25999668

  15. Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis

    PubMed Central

    Surapaneni, Krishna Mohan; Jainu, Mallika

    2014-01-01

    Background: Non alcoholic steatohepatitis (NASH), severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD). It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. Objective: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH). Materials and Methods: Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and γ-Glutamyl Transferase (GGT) were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH. Results: The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2) when compared to rats in control group (group 1). Conclusion: It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also confers protection to some extent against NASH. PMID:24761121

  16. Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function

    PubMed Central

    Groebner, Jennifer L.; Fernandez, David J.; Tuma, Dean J.; Tuma, Pamela L.

    2016-01-01

    Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to micro-tubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease. PMID:25148871

  17. Acute Alcohol Drinking Promotes Piecemeal Percepts during Binocular Rivalry

    PubMed Central

    Cao, Dingcai; Zhuang, Xiaohua; Kang, Para; Hong, Sang W.; King, Andrea C.

    2016-01-01

    Binocular rivalry refers to perceptual alternation when two eyes view different images. One of the potential percepts during binocular rivalry is a spatial mosaic of left- and right-eye images, known as piecemeal percepts, which may result from localized rivalries between small regions in the left- and right-eye images. It is known that alcohol increases inhibitory neurotransmission, which may reduce the number of alternations during binocular rivalry. However, it is unclear whether alcohol affects rivalry dynamics in the same manner for both coherent percepts (i.e., percepts of complete left or right images) and piecemeal percepts. To address this question, the present study measured the dynamics of binocular rivalry before and after 15 moderate-to-heavy social drinkers consumed an intoxicating dose of alcohol versus a placebo beverage. Both simple rivalrous stimuli consisting of gratings with different orientations, and complex stimuli consisting of a face or a house were tested to examine alcohol effects on rivalry as a function of stimulus complexity. Results showed that for both simple and complex stimuli, alcohol affects coherent and piecemeal percepts differently. More specifically, alcohol reduced the number of coherent percepts but not the mean dominance duration of coherent percepts. In contrast, for piecemeal percepts, alcohol increased the mean dominance duration but not the number of piecemeal percepts. These results suggested that alcohol drinking may selectively affect the dynamics of transitional period of binocular rivalry by increasing the duration of piecemeal percepts, leading to a reduction in the number of coherent percepts. The differential effect of alcohol on the dynamics of coherent and piecemeal percepts cannot be accounted for by alcohol’s effect on a common inhibitory mechanism. Other mechanisms, such as increasing neural noise, are needed to explain alcohol’s effect on the dynamics of binocular rivalry. PMID:27092096

  18. Acute alcohol effects on narrative recall and contextual memory: an examination of fragmentary blackouts.

    PubMed

    Wetherill, Reagan R; Fromme, Kim

    2011-08-01

    The present study examined the effects of alcohol consumption on narrative recall and contextual memory among individuals with and without a history of fragmentary blackouts in an attempt to better understand why some individuals experience alcohol-induced memory impairments whereas others do not, even at comparable blood alcohol concentrations (BACs). Standardized beverage (alcohol and no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context memory performance before and after alcohol consumption in individuals with (n=44) and without (n=44) a history of fragmentary blackouts. Findings indicate that acute alcohol intoxication led to impairments in free recall, but not next-day cued recall. Further, participants showed similar memory performance when sober, but individuals who consumed alcohol and had a positive history of fragmentary blackouts showed greater contextual memory impairments than those who had not previously experienced a fragmentary blackout. Thus, it appears that some individuals may have an inherent vulnerability to alcohol-induced memory impairments due to alcohol's effects on contextual memory processes. PMID:21497445

  19. Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats

    PubMed Central

    Ye, Qinyuan; Lian, Fuzhi; Chavez, Pollyanna R.G.; Chung, Jayong; Ling, Wenhua; Qin, Hua; Seitz, Helmut K.

    2012-01-01

    Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which is associated with hepatocarcinogenesis. We investigated whether treatment with chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated hepatic carcinogenesis in rats. Rats were fed either an ethanol liquid diet or a non-ethanol liquid diet, with or without CMZ for one and ten months. A single intraperitoneal injection of diethylnitrosamine (DEN, 20 mg/kg) was given to initiate hepatic carcinogenesis. CYP2E1 expression, inflammatory proteins, cell proliferation, protein-bound 4-HNE, etheno-DNA adducts, 8-hydroxy-2'-deoxyguanosine (8-OHdG), retinoid concentrations, and hepatic carcinogenesis were examined. Ethanol feeding for 1 month with DEN resulted in significantly increased hepatic CYP2E1 levels and increased nuclear accumulation of NF-κB protein and TNF-α expression, which were associated with increased cyclin D1 expression and p-GST positive altered hepatic foci. All of these changes induced by ethanol feeding were significantly inhibited by the one month CMZ treatment. At 10-months of treatment, hepatocellular adenomas were detected in ethanol-fed rats only, but neither in control rats nor in animals receiving ethanol and CMZ. The 8-OHdG formation was found to be significantly increased in ethanol fed animals and normalized with CMZ treatment. In addition, alcohol-reduced hepatic retinol and retinoic acid concentrations were restored by CMZ treatment to normal levels in the rats at 10 months of treatment. These data demonstrate that the inhibition of ethanol-induced CYP2E1 as a key pathogenic factor can counteract the tumor-promoting action of ethanol by decreasing TNF-α expression, NF-κB activation, and oxidative DNA damage as well as restoring normal hepatic levels of retinoic acid in DEN-treated rats. PMID:23543859

  20. Acute cholestatic hepatitis caused by amoxicillin/clavulanate.

    PubMed

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

    2013-12-14

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

  1. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect

    Wu, Weibin; Institutes of Biomedical Science, Fudan University, Shanghai 200032 ; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin; Institutes of Biomedical Science, Fudan University, Shanghai 200032

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  2. Hepatitis

    MedlinePlus

    ... Issues Listen Español Text Size Email Print Share Hepatitis Page Content Article Body Hepatitis means “inflammation of ... it has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool ...

  3. Post-Acute Coronary Syndrome Alcohol Abuse: Prospective Evaluation in the ERICO Study

    PubMed Central

    Morilha, Abner; Karagulian, Samuel; Lotufo, Paulo A.; Santos, Itamar S.; Benseñor, Isabela M.; Goulart, Alessandra C.

    2015-01-01

    Background Some studies have indicated alcohol abuse as one of the contributors to the development of cardiovascular disease, particularly coronary heart disease. However, this relationship is controversial. Objective To investigate the relationship between post-acute coronary syndrome (ACS) alcohol abuse in the Acute Coronary Syndrome Registry Strategy (ERICO Study). Methods 146 participants from the ERICO Study answered structured questionnaires and underwent laboratory evaluations at baseline, 30 days and 180 days after ACS. The Alcohol Use Disorders Identification Test (AUDIT) was applied to assess harmful alcohol consumption in the 12 months preceding ACS (30 day-interview) and six months after that. Results The frequencies of alcohol abuse were 24.7% and 21.1% in the 12 months preceding ACS and six months after that, respectively. The most significant cardiovascular risk factors associated with high-risk for alcohol abuse 30 days after the acute event were: male sex (88.9%), current smoking (52.8%) and hypertension (58.3%). Six months after the acute event, the most significant results were replicated in our logistic regression, for the association between alcohol abuse among younger individuals [35-44 year-old multivariate OR: 38.30 (95% CI: 1.44-1012.56) and 45-54 year-old multivariate OR: 10.10 (95% CI: 1.06-96.46)] and for smokers [current smokers multivariate OR: 51.09 (95% CI: 3.49-748.01) and past smokers multivariate OR: 40.29 (95% CI: 2.37-685.93)]. Conclusion Individuals younger than 54 years and smokers showed a significant relation with harmful alcohol consumption, regardless of the ACS subtype. PMID:26131701

  4. Hepatic cannabinoid receptor type 1 mediates alcohol-induced regulation of bile acid enzyme genes expression via CREBH.

    PubMed

    Chanda, Dipanjan; Kim, Yong-Hoon; Li, Tiangang; Misra, Jagannath; Kim, Don-Kyu; Kim, Jung Ran; Kwon, Joseph; Jeong, Won-Il; Ahn, Sung-Hoon; Park, Tae-Sik; Koo, Seung-Hoi; Chiang, John Y L; Lee, Chul-Ho; Choi, Hueng-Sik

    2013-01-01

    Bile acids concentration in liver is tightly regulated to prevent cell damage. Previous studies have demonstrated that deregulation of bile acid homeostasis can lead to cholestatic liver disease. Recently, we have shown that ER-bound transcription factor Crebh is a downstream effector of hepatic Cb1r signaling pathway. In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process. We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo alongwith significant increase in Crebh gene expression and activation. Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis. Overexpression of Crebh increased the expression of key bile acid synthesis enzyme genes via direct binding of Crebh to their promoters, whereas Cb1r knockout and Crebh-knockdown mice were protected against alcohol-induced perturbation of bile acid homeostasis. Interestingly, insulin treatment protected against Cb1r-mediated Crebh-induced disruption of bile acid homeostasis. Furthermore, Crebh expression and activation was found to be markedly increased in insulin resistance conditions and Crebh knockdown in diabetic mice model (db/db) significantly reversed alcohol-induced disruption of bile acid homeostasis. Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis. PMID:23894352

  5. Extraordinary cause of acute gastric dilatation and hepatic portal venous gas: Chronic use of synthetic cannabinoid

    PubMed Central

    Sevinc, Mert Mahsuni; Kinaci, Erdem; Bayrak, Savas; Yardimci, Aytul Hande; Cakar, Ekrem; Bektaş, Hasan

    2015-01-01

    Addiction to synthetic cannabinoids (SCs) is a growing social and health problem worldwide. Chronic use of SCs may cause adverse effects in the gastrointestinal system. We describe a very rare case of acute gastric dilatation (AGD) and hepatic portal venous gas (HPVG), with findings of acute abdomen resulting from chronic use of a SC, Bonzai. AGD and HPVG were detected by computerized tomography examination. Patchy mucosal ischemia was seen in endoscopic examination. Despite the findings of an acute abdomen, a non-surgical approach with nasogastric decompression, antibiotic therapy, and close radiologic and endoscopic follow-up was preferred in the presented case. Clinical and radiologic findings decreased dramatically on the first day, and endoscopic findings gradually disappeared over 7 d. In conclusion, this case shows that chronic use of a SC may cause AGD and accompanying HPVG, which can be managed non-surgically despite the findings of acute abdomen. PMID:26457032

  6. The Clinical Course of Cirrhosis Patients Hospitalized for Acute Hepatic Deterioration: A Prospective Bicentric Study.

    PubMed

    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. PMID:26632701

  7. Adolescents and alcohol: acute sensitivities, enhanced intake, and later consequences.

    PubMed

    Spear, Linda Patia

    2014-01-01

    Adolescence is an evolutionarily conserved developmental period characterized by notable maturational changes in the brain along with various age-related behavioral characteristics, including the propensity to initiate alcohol and other drug use and consume more alcohol per occasion than adults. After a brief review of adolescent neurobehavioral function from an evolutionary perspective, the paper will turn to assessment of adolescent alcohol sensitivity and consequences, with a focus on work from our laboratory. After summarizing evidence showing that adolescents differ considerably from adults in their sensitivity to various effects of alcohol, potential contributors to these age-typical sensitivities will be discussed, and the degree to which these findings are generalizable to other drugs and to human adolescents will be considered. Recent studies are then reviewed to illustrate that repeated alcohol exposure during adolescence induces behavioral, cognitive, and neural alterations that are highly specific, replicable, persistent and dependent on the timing of the exposure. Research in this area is in its early stages, however, and more work will be necessary to characterize the extent of these neurobehavioral alterations and further determine the degree to which observed effects are specific to alcohol exposure during adolescence. PMID:24291291

  8. Acute hepatitis A in Italy: incidence, risk factors and preventive measures.

    PubMed

    Tosti, M E; Spada, E; Romanò, L; Zanetti, A; Mele, A

    2008-10-01

    The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by using data collected from the Italian surveillance system of acute viral hepatitis (SEIEVA). To this end, a case-control study within a population-based surveillance for acute viral hepatitis was performed. AHA incidence has been estimated since 1991; the association with considered risk factors was analysed from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a peak during 1996-1998 due to an outbreak in southern Italy. The incidence of AHA was highest among persons aged 15-24 years. The case-fatality rate was 2.9 / 10 000. Contact with individuals with AHA [adjusted OR (OR(adj)) = 3.8, 95% CI 2.7-5.5; population-attributable risk (PAR) = 7.5%], travelling to endemic areas (OR(adj) = 3.1, 95% CI = 2.6-3.8; PAR = 19.5%), ingestion of raw shellfish (OR(adj) = 1.8, 95% CI = 1.6-2.1; PAR = 26.6%), and cohabitation with day care children (OR(adj) = 1.3, 95% CI = 1.01-1.7; PAR = 2.3%) were the main important risk factors. In 2003, an outbreak, with high case-fatality rate occurred among intravenous drug users, in a central Italian town. A weak association was found for male homosexuality when acute hepatitis C cases were employed as controls (OR(adj) = 1.4 CI, 95% CI = 1.1-1.9). Hepatitis A virus infections are currently occurring more frequently in adults, in whom the disease is most severe. In conclusion, looking at the attributable risks, at present most of the AHA infections are due to shellfish consumption, travel to endemic areas and contact with patients with AHA. Vaccination of individuals at increased risk of infection, as well as persons with underling liver disease and those at increased risk of complications, combined with surveillance of shellfish retail outlets are efficient control measures. PMID:18837830

  9. Chronic alcohol intake up-regulates hepatic expressions of carotenoid cleavage enzymes and peroxisomal proliferator-activated receptors in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism.Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15’-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9910’-monooxygenase 2 (CMO2)...

  10. Acute hepatitis C in the Netherlands: characteristics of the epidemic in 2014.

    PubMed

    Hullegie, S J; van den Berk, G E L; Leyten, E M S; Arends, J E; Lauw, F N; van der Meer, J T M; Posthouwer, D; van Eeden, A; Koopmans, P P; Richter, C; van Kasteren, M E E; Kroon, F P; Bierman, W F W; Groeneveld, P H P; Lettinga, K D; Soetekouw, R; Peters, E J G; Verhagen, D W M; van Sighem, A I; Claassen, M A A; Rijnders, B J A

    2016-02-01

    Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt. PMID:26482267

  11. Liver receptor homolog 1 is a negative regulator of the hepatic acute-phase response.

    PubMed

    Venteclef, Nicolas; Smith, Jason C; Goodwin, Bryan; Delerive, Philippe

    2006-09-01

    The orphan nuclear receptor liver receptor homolog 1 (LRH-1) has been reported to play an important role in bile acid biosynthesis and reverse cholesterol transport. Here, we show that LRH-1 is a key player in the control of the hepatic acute-phase response. Ectopic expression of LRH-1 with adenovirus resulted in strong inhibition of both interleukin-6 (IL-6)- and IL-1beta-stimulated haptoglobin, serum amyloid A, and fibrinogen beta gene expression in hepatocytes. Furthermore, induction of the hepatic inflammatory response was significantly exacerbated in HepG2 cells expressing short hairpin RNA targeting LRH-1 expression. Moreover, transient-transfection experiments and electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that LRH-1 regulates this cytokine-elicited inflammatory response by, at least in part, antagonizing the CCAAT/enhancer binding protein beta signaling pathway. Finally, we show, by using LRH-1 heterozygous mice, that LRH-1 is involved in the control of the inflammatory response at the hepatic level in vivo. Taken together, our results outline an unexpected role for LRH-1 in the modulation of the hepatic acute-phase response. PMID:16943422

  12. Case Report: Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E

    PubMed Central

    Moisset, Xavier; Vitello, Nicolas; Bicilli, Elodie; Courtin, Romain; Ferrier, Anna; Taithe, Frederic; Lahaye, Clément; Hssain, Ali Ait; Garrouste, Cyril; Pierre, Clavelou

    2014-01-01

    Introduction: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers. Case report: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding.  A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months. Conclusion: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has  not yet been determined. PMID:24555112

  13. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

    PubMed

    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. PMID:26164743

  14. Acute Hepatitis after Ingestion of a Preparation of Chinese Skullcap and Black Catechu for Joint Pain

    PubMed Central

    Papafragkakis, Charilaos; Ona, Mel A.; Reddy, Madhavi; Anand, Sury

    2016-01-01

    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. PMID:27144042

  15. Linoleic Acid Induced Acute Hepatitis: A Case Report and Review of the Literature

    PubMed Central

    Bilal, Mohammad; Patel, Yogesh; Burkitt, Micheal; Babich, Michael

    2015-01-01

    Several dietary supplements used for weight loss have been reported to cause hepatotoxicity. Conjugated Linoleic Acid (CLA) is a dietary supplement that has been shown to cause reduction in body fat mass. Here, we present the first case of CLA induced acute hepatitis in the United States and only the third case in the worldwide literature along with a brief review of the literature. PMID:26240766

  16. A valuable antigen detection method for diagnosis of acute hepatitis E.

    PubMed

    Wen, Gui-Ping; Tang, Zi-Min; Yang, Fan; Zhang, Ke; Ji, Wen-Fang; Cai, Wei; Huang, Shou-Jie; Wu, Ting; Zhang, Jun; Zheng, Zi-Zheng; Xia, Ning-Shao

    2015-03-01

    Hepatitis E virus (HEV) is a serious public health problem. The commonly used tests that are specific for current HEV infection diagnosis include the detection of anti-HEV IgM and HEV RNA. Here, we report an improved enzyme-linked immunosorbent assay (ELISA) method for HEV antigen detection with a linear range equivalent to 6.3 × 10(3) to 9.2 × 10(5) RNA copies per ml. The monoclonal antibody (MAb) 12F12, a high-ability MAb that binds HEV virus, was selected as the capture antibody from a panel of 95 MAbs. The positive period of HEV antigenemia in infected monkeys using this test was, on average, 3 weeks longer than previously reported and covered the majority of the acute phase. The positive detection rates of IgM, RNA, and new antigen from the first serum samples collected from 16 confirmed acute hepatitis E patients were 81% (13/16), 81% (13/16), and 100% (16/16), respectively. In three patients, the initial serum specimens that tested negative for IgM, despite the presence of symptoms of acute hepatitis and elevated alanine aminotransferase (ALT) levels, were positive for HEV antigen and HEV RNA. In contrast, the serum samples of the three RNA-negative patients were antigen positive (and IgM positive), possibly due to the degradation of HEV nucleic acids. Our results suggest that this new antigen detection method has acceptable concordance with RNA detection and could serve as an important tool for diagnosing acute hepatitis E. PMID:25540394

  17. Animated bird silhouette above the tank: Acute alcohol diminishes fear responses in zebrafish

    PubMed Central

    Luca, Ruxandra M.; Gerlai, Robert

    2012-01-01

    Alcohol dependence and alcohol abuse represent major unmet medical needs. The zebrafish is considered to be a promising vertebrate species with which the effects of alcohol on brain function and behavior and the mechanisms underlying these effects may be studied. Alcohol is known to induce alterations in motor function as well as fear and anxiety. Here we present a recently developed fear paradigm in which we employ an animated (moving) image of a bird silhouette. We measure the effect of acute alcohol administration (dose range employed: 0.00 – 0.75 vol/vol percentage, bath exposure for 60 minutes) on the behavioral responses of zebrafish. We test these responses during a pre-stimulus, stimulus and post-stimulus period of the task using both a video-tracking and an observation based quantification method. The fear inducing stimulus was found to decrease the distance of the zebrafish from the bottom of the tank, to increase number of erratic movements, and to increase the number of jumps in alcohol exposed fish (versus control fish). Alcohol attenuated these fear responses in a dose dependent manner. In addition, alcohol decreased general activity at the highest dose, an effect that was independent of the presentation of the stimulus. We discuss the similarities and differences between observation and video-tracking based results and conclude that fear paradigms will be useful in revealing alcohol induced functional changes in the brain of zebrafish. PMID:22266470

  18. Sustained Hyperresponsiveness of Dendritic Cells Is Associated with Spontaneous Resolution of Acute Hepatitis C

    PubMed Central

    Pelletier, Sandy; Bédard, Nathalie; Said, Elias; Ancuta, Petronela; Bruneau, Julie

    2013-01-01

    Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV infection and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infection were studied: an uninfected group, a group with acute HCV infection with spontaneous resolution, and a group with acute infection with chronic evolution. We examined the frequency, maturation status, and cytokine production capacity of DCs in response to the Toll-like receptor 4 (TLR4) and TLR7/8 ligands lipopolysaccharide (LPS) and single-stranded RNA (ssRNA), respectively. Several observations could distinguish HCV-negative IDUs and acute HCV resolvers from patients with acute infection with chronic evolution. First, we observed a decrease in the frequency of mature CD86+, programmed death-1 receptor ligand-positive (PDL1+), and PDL2+ pDCs. This phenotype was associated with the increased sensitivity of pDCs from resolvers and HCV-negative IDUs versus the group with acute infection with chronic evolution to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV-negative IDUs produced higher levels of cytokines than mDCs from the group with acute infection with chronic evolution. Third, mDCs from all patients with acute HCV infection, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA than mDCs from healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that the immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection. PMID:23576504

  19. Sustained hyperresponsiveness of dendritic cells is associated with spontaneous resolution of acute hepatitis C.

    PubMed

    Pelletier, Sandy; Bédard, Nathalie; Said, Elias; Ancuta, Petronela; Bruneau, Julie; Shoukry, Naglaa H

    2013-06-01

    Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV infection and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infection were studied: an uninfected group, a group with acute HCV infection with spontaneous resolution, and a group with acute infection with chronic evolution. We examined the frequency, maturation status, and cytokine production capacity of DCs in response to the Toll-like receptor 4 (TLR4) and TLR7/8 ligands lipopolysaccharide (LPS) and single-stranded RNA (ssRNA), respectively. Several observations could distinguish HCV-negative IDUs and acute HCV resolvers from patients with acute infection with chronic evolution. First, we observed a decrease in the frequency of mature CD86(+), programmed death-1 receptor ligand-positive (PDL1(+)), and PDL2(+) pDCs. This phenotype was associated with the increased sensitivity of pDCs from resolvers and HCV-negative IDUs versus the group with acute infection with chronic evolution to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV-negative IDUs produced higher levels of cytokines than mDCs from the group with acute infection with chronic evolution. Third, mDCs from all patients with acute HCV infection, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA than mDCs from healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that the immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection. PMID:23576504

  20. Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats

    PubMed Central

    Hussein, Osamah; Grosovski, Masha; Lasri, Etti; Svalb, Sergio; Ravid, Uzi; Assy, Nimer

    2007-01-01

    AIM: To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group (n = 8) were on chow diet (Group 1), rats (n = 6) on methionine choline-deficient diet (MCDD) (Group 2), rats (n = 6) on MCDD enriched with olive oil (Group 3), rats (n = 6) on MCDD with fish oil (Group 4) and rats (n = 6) on MCDD with butter fat (Group 5). After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters. RESULTS: The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups, but not in MCDD and MCDD + olive oil groups. The increase in hepatic triglycerides (TG) levels was blunted by 30% in MCDD + olive oil group (0.59 ± 0.09) compared with MCDD group (0.85 ± 0.04, p < 0.004), by 37% compared with MCDD + fish oil group (0.95 ± 0.07, p < 0.001), and by 33% compared with MCDD + butter group (0.09 ± 0.1, p < 0.01). The increase in serum TG was lowered by 10% in MCDD + olive oil group (0.9 ± 0.07) compared with MCDD group (1.05 ± 0.06). Hepatic cholesterol increased by 15-fold in MCDD group [(0.08 ± 0.02, this increment was blunted by 21% in MCDD + fish oil group (0.09 ± 0.02)]. In comparison with the control group, ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD + olive oil, MCDD + fish oil and MCDD + butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group (1.58 ± 0.08), hepatic MDA contents in MCDD + olive oil (3.3 ± 0.6), MCDD + fish oil (3.0 ± 0.4), and MCDD + butter group (2.9 ± 0.36) were increased by 108%, 91% and 87%, respectively (p < 0.004). Hepatic paraoxonase activity decreased significantly in all treatment groups, mostly with MCDD + olive oil group (-68%). CONCLUSION: Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD, but does not provide the greatest antioxidant activity. PMID:17230603

  1. Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

    PubMed Central

    O’Malley, Stephanie S.; Gueorguieva, Ralitza; Wu, Ran; Jatlow, Peter I.

    2015-01-01

    Background Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods 18 healthy individuals (8 cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL, in random order in 3 laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45 am prior to drinking, at 2 pm, and at 7:45 the next morning. Mixed effects regression models compared baseline and 24 hr. post-drinking bilirubin concentrations. Results Total serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24 hours in non-smokers (from Mean=0.38, SD=0.24 to Mean=0.51 SD=0.30, F(1, 32.2) =24.24, p<.0001) but not in smokers (from Mean=0.25, SD=0.12 to Mean=0.26, SD=0.15, F(1, 31.1) =0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. Conclusions Alcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies. PMID:25707709

  2. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

    2015-10-01

    The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management. PMID:25500531

  3. Increases in Acute Hepatitis B Virus Infections - Kentucky, Tennessee, and West Virginia, 2006-2013.

    PubMed

    Harris, Aaron M; Iqbal, Kashif; Schillie, Sarah; Britton, James; Kainer, Marion A; Tressler, Stacy; Vellozzi, Claudia

    2016-01-01

    As many as 2.2 million persons in the United States are chronically infected with hepatitis B virus (HBV) (1), and approximately 15%-25% of persons with chronic HBV infection will die prematurely from cirrhosis or liver cancer (2). Since 2006, the overall U.S. incidence of acute HBV infection has remained stable; the rate in 2013 was 1.0 case per 100,000 persons (3). Hepatitis B vaccination is highly effective in preventing HBV infection and is recommended for all infants (beginning at birth), all adolescents, and adults at risk for HBV infection (e.g., persons who inject drugs, men who have sexual contact with men, persons infected with human immunodeficiency virus [HIV], and others). Hepatitis B vaccination coverage is low among adults: 2013 National Health Interview Survey data indicated that coverage with ≥3 doses of hepatitis B vaccine was 32.6% for adults aged 19-49 years (4). Injection drug use is a risk factor for both hepatitis C virus (HCV) and HBV. Among young adults in some rural U.S. communities, an increased incidence of HCV infection has been associated with a concurrent increase of injection drug use (5); and recent data indicate an increase of acute HCV infection in the Appalachian region associated with injection drug use (6). Using data from the National Notifiable Diseases Surveillance System (NNDSS) during 2006-2013, CDC assessed the incidence of acute HBV infection in three of the four Appalachian states (Kentucky, Tennessee, and West Virginia) included in the HCV infection study (6). Similar to the increase of HCV infections recently reported, an increase in incident cases of acute HBV infection in these three states has occurred among non-Hispanic whites (whites) aged 30-39 years who reported injection drug use as a common risk factor. Since 2009, cases of acute HBV infection have been reported from more non-urban than urban regions. Evidence-based services to prevent HBV infection are needed. PMID:26821369

  4. Is rat liver affected by non-alcoholic steatosis more susceptible to the acute toxic effect of thioacetamide?

    PubMed Central

    Kučera, Otto; Lotková, Halka; Staňková, Pavla; Podhola, Miroslav; Roušar, Tomáš; Mezera, Vojtěch; Červinková, Zuzana

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition of the liver in the western world. There is only little evidence about altered sensitivity of steatotic liver to acute toxic injury. The aim of this project was to test whether hepatic steatosis sensitizes rat liver to acute toxic injury induced by thioacetamide (TAA). Male Sprague–Dawley rats were fed ad libitum a standard pelleted diet (ST-1, 10% energy fat) and high-fat gelled diet (HFGD, 71% energy fat) for 6 weeks and then TAA was applied intraperitoneally in one dose of 100 mg/kg. Animals were sacrificed in 24-, 48- and 72-h interval after TAA administration. We assessed the serum biochemistry, the hepatic reduced glutathione, thiobarbituric acid reactive substances, cytokine concentration, the respiration of isolated liver mitochondria and histopathological samples (H+E, Sudan III, bromodeoxyuridine [BrdU] incorporation). Activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and concentration of serum bilirubin were significantly higher in HFGD groups after application of TAA, compared to ST-1. There were no differences in activities of respiratory complexes I and II. Serum tumour necrosis factor alpha at 24 and 48 h, liver tissue interleukin-6 at 72 h and transforming growth factor β1 at 24 and 48 h were elevated in TAA-administrated rats fed with HFGD, but not ST-1. TAA-induced centrilobular necrosis and subsequent regenerative response of the liver were higher in HFGD-fed rats in comparison with ST-1. Liver affected by NAFLD, compared to non-steatotic liver, is more sensitive to toxic effect of TAA. PMID:21410800

  5. Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis.

    PubMed

    Wang, Qian; Du, Jianjun; Yu, Pengfei; Bai, Bin; Zhao, Zhanwei; Wang, Shiqi; Zhu, Junjie; Feng, Quanxin; Gao, Yun; Zhao, Qingchuan; Liu, Chaoxu

    2015-01-01

    Hepatic steatosis (HS) can exacerbate acute pancreatitis (AP). This study aimed to investigate the relation between α1-antitrypsin (AAT) and acute pancreatitis when patients have HS. Using proteomic profiling, we identified 18 differently expressed proteins pots in the serum of rats with or without HS after surgical establishment of AP. AAT was found to be one of the significantly down-regulated proteins. AAT levels were significantly lower in hepatic steatosis acute pancreatitis (HSAP) than in non-HSAP (NHSAP) (P < 0.001). To explore the clinical significance of these observations, we measured the levels of AAT in the serum of 240 patients with HSAP, NHSAP, fatty liver disease (FLD), or no disease. Compared with healthy controls, serum AAT levels in patients with NHSAP were significantly higher (P < 0.01), while in patients with HSAP serum AAT levels were significantly lower (P < 0.01). Further studies showed that acute physiology and chronic health evaluation (APACHE-II) scores were negatively correlated with serum AAT levels (r = -0.85, P < 0.01). In conclusion, low serum levels of AAT in patients with HSAP are correlated with disease severity and AAT may represent a potential target for therapies aiming to improve pancreatitis. PMID:26634430

  6. Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis

    PubMed Central

    Wang, Qian; Du, Jianjun; Yu, Pengfei; Bai, Bin; Zhao, Zhanwei; Wang, Shiqi; Zhu, Junjie; Feng, Quanxin; Gao, Yun; Zhao, Qingchuan; Liu, Chaoxu

    2015-01-01

    Hepatic steatosis (HS) can exacerbate acute pancreatitis (AP). This study aimed to investigate the relation between α1-antitrypsin (AAT) and acute pancreatitis when patients have HS. Using proteomic profiling, we identified 18 differently expressed proteins pots in the serum of rats with or without HS after surgical establishment of AP. AAT was found to be one of the significantly down-regulated proteins. AAT levels were significantly lower in hepatic steatosis acute pancreatitis (HSAP) than in non-HSAP (NHSAP) (P < 0.001). To explore the clinical significance of these observations, we measured the levels of AAT in the serum of 240 patients with HSAP, NHSAP, fatty liver disease (FLD), or no disease. Compared with healthy controls, serum AAT levels in patients with NHSAP were significantly higher (P < 0.01), while in patients with HSAP serum AAT levels were significantly lower (P < 0.01). Further studies showed that acute physiology and chronic health evaluation (APACHE-II) scores were negatively correlated with serum AAT levels (r = −0.85, P < 0.01). In conclusion, low serum levels of AAT in patients with HSAP are correlated with disease severity and AAT may represent a potential target for therapies aiming to improve pancreatitis. PMID:26634430

  7. Cross-genotype-specific T-cell responses in acute hepatitis E virus (HEV) infection.

    PubMed

    Gisa, A; Suneetha, P V; Behrendt, P; Pischke, S; Bremer, B; Falk, C S; Manns, M P; Cornberg, M; Wedemeyer, H; Kraft, A R M

    2016-04-01

    Hepatitis E is an inflammatory liver disease caused by infection with the hepatitis E virus (HEV). In tropical regions, HEV is highly endemic and predominantly mediated by HEV genotypes 1 and 2 with >3 million symptomatic cases per year and around 70 000 deaths. In Europe and America, the zoonotic HEV genotypes 3 and 4 have been reported with continues increasing new infections per year. So far, little is known about T-cell responses during acute HEV genotype 3 infection. Therefore, we did a comprehensive study investigating HEV-specific T-cell responses using genotypes 3- and 1-specific overlapping peptides. Additional cytokines and chemokines were measured in the plasma. In four patients, longitudinal studies were performed. Broad functional HEV-specific CD4(+) and CD8(+) T-cell responses were detectable in patients acutely infected with HEV genotype 3. Elevated of pro- and anti-inflammatory cytokine levels during acute HEV infection correlated with ALT levels. Memory HEV-specific T-cell responses were detectable up to >1.5 years upon infection. Importantly, cross-genotype HEV-specific T-cell responses (between genotypes 1 and 3) were measurable in all investigated patients. In conclusion, we could show for the first time HEV-specific T-cell responses during and after acute HEV genotype 3 infection. Our data of cross-genotype HEV-specific T-cell responses might suggest a potential role in cross-genotype-specific protection between HEV genotypes 1 and 3. PMID:26852892

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

    PubMed Central

    Sagnelli, Evangelista; Sagnelli, Caterina; Pisaturo, Mariantonietta; Macera, Margherita; Coppola, Nicola

    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 in 1984 to 0.85/100000 in 2012, and by the reduced prevalence of hepatitis B surface antigen (HBsAg)-positive cases among chronic hepatitis patients with different etiologies, from 60% in 1975 to about 10% in 2001. The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3% in the 1980s to 1% in 2010. Linked to HBV by its characteristics of defective virus, the hepatitis delta virus (HDV) has shown a similar epidemiological impact on the Italian population over time. The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from 24% in 1990 to 8.5% in 2006. Before the beneficial effects of HBV mass vaccination introduced in 1991, the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations, the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size. A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds. PMID:24976701

  9. Acute Alcohol Effects on Repetition Priming and Word Recognition Memory with Equivalent Memory Cues

    ERIC Educational Resources Information Center

    Ray, Suchismita; Bates, Marsha E.

    2006-01-01

    Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of words…

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

    PubMed

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

    2015-09-01

    Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds. PMID:25458485

  11. Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013.

    PubMed

    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. J. Med. Virol. 88:622-630, 2016. © 2015 Wiley Periodicals, Inc. PMID:26369542

  12. Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol

    PubMed Central

    Trim, Ryan S.; Simmons, Alan N.; Tolentino, Neil J.; Hall, Shana A.; Matthews, Scott C.; Robinson, Shannon K.; Smith, Tom L.; Padula, Claudia B.; Paulus, Martin P.; Tapert, Susan F.; Schuckit, Marc A.

    2013-01-01

    Background A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk for alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. Methods 30 matched high- and low-LR pairs (N=60 healthy young adults) were recruited from the University of California, San Diego and administered a structured diagnostic interview and laboratory alcohol challenge followed by two fMRI sessions under placebo and alcohol conditions, in randomized order. Task performance and BOLD response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task was examined across 120 fMRI sessions. Results Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p<.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. Conclusions Alcohol had differential effects on brain activation for low and high LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR, and identify brain regions that may be associated with the low LR response. PMID:20477775

  13. Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

    PubMed Central

    Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

    2015-01-01

    Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their intricate differences with chronic patients which should be useful from the clinical point of view. PMID:26571502

  14. Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report

    PubMed Central

    Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

    2015-01-01

    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 21st 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. PMID:26327776

  15. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease.

    PubMed

    Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

    2014-01-01

    Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients. PMID:24269813

  16. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  17. Synaptic membrane responses to acute and chronic alcohol intoxication in high alcohol sensitive (HAS) and low alcohol sensitive (LAS) selectively bred rats.

    PubMed

    Beaugé, F; Kerfriden, G; Ménez, J F; Aufrère, G; Le Bourhis, B

    1994-11-01

    HAS (high alcohol sensitive) and LAS (low alcohol sensitive) lines of rats have been selectively bred based on their differences in ethanol-induced sleep time. In the present study, the two lines were compared to examine another central effect of acute alcohol intoxication: namely, hypothermia. As the disturbances in membrane microorganization have been associated with the nervous system's sensitivity and tolerance to ethanol, the synaptic plasma membrane fluidity and acute sensitivity to ethanol were also evaluated by fluorescence polarization of DPH probes in the HAS and LAS rats. The two lines did not differ in the magnitude of their hypothermic response after acute injection of ethanol (3 g/kg body wt, i.p.). Although membranes in the HAS line were slightly more rigid than in the LAS line, the level of membrane disordering after acute ethanol addition was identical for the two lines in the region examined with the DPH probe. Following the chronic intoxication of the rats, the two lines developed tolerance to the hypnotic and hypothermic effects of ethanol. In the same way, a membrane resistance (i.e. tolerance) to the disordering effect of acute ethanol addition developed in the region probed with DPH. In general, the LAS line showed a more pronounced level of tolerance than the HAS line at both the functional and membrane level. These results suggest that different measures used to assess the depressant action of ethanol, such as sleep time, hypothermia or membrane disordering, may not be related and could indicate different genetic origins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7695793

  18. Aldehyde Dehydrogenase-2 (ALDH2) Ameliorates Chronic Alcohol Ingestion-Induced Hepatic Steatosis and Inflammation: Role of Autophagy

    PubMed Central

    Guo, Rui; Xu, Xihui; Babcock, Sara A.; Zhang, Yingmei; Ren, Jun

    2014-01-01

    Background & Aims Mitochondrial aldehyde dehydrogenase (ALDH2) plays a critical role in the detoxification of the ethanol metabolite acetaldehyde. This study was designed to examine the impact of global ALDH2 overexpression on alcohol-induced hepatic steatosis. Methods Wild-type friendly virus B (FVB) and ALDH2 transgenic mice were placed on a 4% alcohol or control diet for 12 weeks. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and cholesterol, hepatic triglyceride, steatosis, fat metabolism-related proteins, pro-inflammatory cytokines, glutathione (GSH), oxidized glutathione (GSSG), autophagy and autophagy signaling were examined. The role of autophagy was evaluated in ADH1-transfected human hepatocellular liver carcinoma cells (VA-13) treated with or without autophagy inducer rapamycin and lysosomal inhibitors. Results Chronic alcohol intake led to elevated AST, ALT, bilirubin, AST/ALT ratio, cholesterol, hepatic triglycerides, hepatic fat deposition as evidenced by H&E and oil Red O staining, associated with disturbed fat metabolism-related proteins (fatty acid synthase, SCD1), upregulated interleukin-6, TNF-α, cyclooxygenase, oxidative stress, and loss of autophagy, the effects of which were attenuated or ablated by ALDH2 transgene. Moreover, ethanol (100 mM) and acetaldehyde (100, 500 μM) increased levels of IL-6 and IFN-γ, and suppressed autophagy in VA-13 cells, the effects of which were markedly alleviated by rapamycin. In addition, lysosomal inhibitors mimicked ethanol-induced p62 accumulation with little additive effect with ethanol. Ethanol significantly suppressed LC3 conversion in the presence of lysosomal inhibitors. Conclusions In summary, our results revealed that ALDH2 plays a beneficial role in ameliorating chronic alcohol intake-induced hepatic steatosis and inflammation through regulation of autophagy. PMID:25457208

  19. Non-alcoholic fatty liver disease (NAFLD) potentiates autoimmune hepatitis in the CYP2D6 mouse model.

    PubMed

    Müller, Peter; Messmer, Marie; Bayer, Monika; Pfeilschifter, Josef M; Hintermann, Edith; Christen, Urs

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) and its more severe development non-alcoholic steatohepatitis (NASH) are increasing worldwide. In particular NASH, which is characterized by an active hepatic inflammation, has often severe consequences including progressive fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Here we investigated how metabolic liver injury is influencing the pathogenesis of autoimmune hepatitis (AIH). We used the CYP2D6 mouse model in which wild type C57BL/6 mice are infected with an Adenovirus expressing the major liver autoantigen cytochrome P450 2D6 (CYP2D6). Such mice display several features of human AIH, including interface hepatitis, formation of LKM-1 antibodies and CYP2D6-specific T cells, as well as hepatic fibrosis. NAFLD was induced with a high-fat diet (HFD). We found that pre-existing NAFLD potentiates the severity of AIH. Mice fed for 12 weeks with a HFD displayed increased cellular infiltration of the liver, enhanced hepatic fibrosis and elevated numbers of liver autoantigen-specific T cells. Our data suggest that a pre-existing metabolic liver injury constitutes an additional risk for the severity of an autoimmune condition of the liver, such as AIH. PMID:26924542

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

    PubMed Central

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

    2015-01-01

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

  1. HIV, Hepatitis C, and Abstinence from Alcohol Among Injection and Non-injection Drug Users.

    PubMed

    Elliott, Jennifer C; Hasin, Deborah S; Stohl, Malka; Des Jarlais, Don C

    2016-03-01

    Individuals using illicit drugs are at risk for heavy drinking and infection with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Despite medical consequences of drinking with HIV and/or HCV, whether drug users with these infections are less likely to drink is unclear. Using samples of drug users in treatment with lifetime injection use (n = 1309) and non-injection use (n = 1996) participating in a large, serial, cross-sectional study, we investigated the associations between HIV and HCV with abstinence from alcohol. About half of injection drug users (52.8 %) and 26.6 % of non-injection drug users abstained from alcohol. Among non-injection drug users, those with HIV were less likely to abstain [odds ratio (OR) 0.55; adjusted odds ratio (AOR) 0.58] while those with HCV were more likely to abstain (OR 1.46; AOR 1.34). In contrast, among injection drug users, neither HIV nor HCV was associated with drinking. However, exploratory analyses suggested that younger injection drug users with HIV or HCV were more likely to drink, whereas older injection drug users with HIV or HCV were more likely to abstain. In summary, individuals using drugs, especially non-injection users and those with HIV, are likely to drink. Age may modify the risk of drinking among injection drug users with HIV and HCV, a finding requiring replication. Alcohol intervention for HIV and HCV infected drug users is needed to prevent further harm. PMID:26080690

  2. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis

    PubMed Central

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I; Serralde-Zúñiga, Aurora E; Cruz-Herrera, Javier; Pérez-Torres, Eduardo; Abdo-Francis, Juan M; Salas-Gordillo, Francisco; Pérez-Hernández, José L

    2015-01-01

    AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). METHODS: This study was an open-label clinical trial, performed at the “Hospital General de México, Dr. Eduardo Liceaga”. We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX. PMID:25945012

  3. Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada

    PubMed Central

    Osiowy, Carla; Giles, Elizabeth; Trubnikov, Max; Choudhri, Yogesh; Andonov, Anton

    2015-01-01

    Objective The prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk. Methods HBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV. Results Nine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections. Conclusion Chronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection. PMID:26406309

  4. Hepatitis E virus infection results in acute graft failure after liver transplantation: a case report.

    PubMed

    Liu, Xiangyan; Shen, Tian; Wang, Zhuoyi; Zhuang, Li; Zhang, Wei; Yu, Jun; Wu, Jian; Zheng, Shusen

    2014-02-01

    Hepatitis E virus (HEV) infection in most individuals is known as a self-limiting, acute, icteric hepatitis, but evidence shows HEV is responsible for choric hepatitis and rapid progressed liver cirrhosis in immuno-compromised patients. We present the case of a patient whose diagnosis of acute graft failure was due to a HEV infection 7 years after his first liver transplantation because of Wilson's disease. The process showed severe jaundice with fatigue, poor appetite and continually rising serum aminopherase. The blood serum was found positive for the anti-HEV IgG antibody but negative for anti-HEV IgM or other infections. Cholangiole cholestasis was detected in graft biopsy. Triple hepato-protective drugs (Transmetil, Polyene Phosphatidylcholine, and Compound Ammonium Glycyrrhetate S) alongside five times Artificial Liver Support System (ALSS) did not improve the patient's condition, but the total bilirubin level rose to more than 900umol/L. So re-transplantation was performed. Blood testing shows normal liver enzymes and bilirubin with persisting anti-HEV IgG antibody positive at the 3-month follow-up. PMID:24518638

  5. Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1α activation

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Szabo, Gyongyi

    2016-01-01

    Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated in livers of alcohol-fed DEN-injected mice compared to controls. In livers with tumors, loss of miR-122 expression with a significant up-regulation of miR-122 target HIF-1α is seen. We conclude that alcoholic steatohepatitis accelerates hepatobiliary tumors with characteristic molecular features of HCC by up-regulating inflammation, cell proliferation, stemness, and miR-122 loss. PMID:26888602

  6. Rhabdomyolysis, acute renal failure, and multiple focal neuropathies after drinking alcohol soaked with centipede.

    PubMed

    Wang, I-Kuan; Hsu, Shih-Pin; Chi, Ching-Chi; Lee, Kam-Fai; Lin, Paul Yann; Chang, Hsueh-Wen; Chuang, Feng-Rong

    2004-01-01

    Many Chinese like to drink alcohol soaked with creatures for promoting health. This study reports a 49-year-old male who presented with multiple focal neuropathies of the upper limbs, coagulopathy, erythematous swelling of the bilateral upper extremities and trunk with bullous skin lesions, and rhabdomyolysis associated with acute renal failure after drinking alcohol soaked with centipede. Soaking a centipede, Scolopendra subspinipes mutilans, in 53% alcohol, produced the wine. Supportive treatment was administered, and the skin lesions and renal failure improved with subsequent neurologic deficit during the week following initial presentation. Alcohol binge or immobilization was the likely cause of neuropathy, bullous skin lesions and rhabdomyolysis in the patient. However, there is a possibility that centipede venom also contributed to the illness in this patient. PMID:15083930

  7. A medical cost estimation with fuzzy neural network of acute hepatitis patients in emergency room.

    PubMed

    Kuo, R J; Cheng, W C; Lien, W C; Yang, T J

    2015-10-01

    Taiwan is an area where chronic hepatitis is endemic. Liver cancer is so common that it has been ranked first among cancer mortality rates since the early 1980s in Taiwan. Besides, liver cirrhosis and chronic liver diseases are the sixth or seventh in the causes of death. Therefore, as shown by the active research on hepatitis, it is not only a health threat, but also a huge medical cost for the government. The estimated total number of hepatitis B carriers in the general population aged more than 20 years old is 3,067,307. Thus, a case record review was conducted from all patients with diagnosis of acute hepatitis admitted to the Emergency Department (ED) of a well-known teaching-oriented hospital in Taipei. The cost of medical resource utilization is defined as the total medical fee. In this study, a fuzzy neural network is employed to develop the cost forecasting model. A total of 110 patients met the inclusion criteria. The computational results indicate that the FNN model can provide more accurate forecasts than the support vector regression (SVR) or artificial neural network (ANN). In addition, unlike SVR and ANN, FNN can also provide fuzzy IF-THEN rules for interpretation. PMID:26153643

  8. Short-term treatment with alcohols causes hepatic steatosis and enhances acetaminophen hepatotoxicity in Cyp2e1(-/-) mice.

    PubMed

    Sinclair, J F; Szakacs, J G; Wood, S G; Walton, H S; Bement, J L; Gonzalez, F J; Jeffery, E H; Wrighton, S A; Bement, W J; Sinclair, P R

    2000-10-15

    CYP2E1 has been reported to have an essential role in alcohol-mediated increases in hepatic steatosis and acetaminophen hepatotoxicity. We found that pretreatment of Cyp2e1(-/-) mice with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, for 7 days resulted in micro- and macrovesicular steatosis in the livers of all mice, as well as a dramatic increase in acetaminophen hepatotoxicity. In Cyp2e1(-/-) mice administered up to 600 mg acetaminophen/kg alone and euthanized 7 h later, there was no increase in serum levels of ALT. In Cyp2e1(-/-) mice pretreated with ethanol and isopentanol, subsequent exposure to 400 or 600 mg acetaminophen/kg resulted in centrilobular necrosis in all mice with maximal elevation in serum levels of ALT. Acetaminophen-mediated liver damage was similar in males and females. Hepatic microsomal levels of APAP activation in untreated females were similar to those in males treated with the alcohols. However, the females, like the males, required pretreatment with the alcohols in order to increase APAP hepatotoxicity. These findings suggest that, in the Cyp2e1(-/-) mice, the alcohol-mediated increase in acetaminophen hepatotoxicity involves the contribution of other factors, in addition to induction of CYP(s) that activate acetaminophen. Alternatively, CYP-mediated activation of acetaminophen measured in vitro may not reflect the actual activity in vivo. Our findings that a 7-day treatment with ethanol and isopentanol causes extensive hepatic steatosis and increases acetaminophen hepatotoxicity in Cyp2e(-/-) mice indicate that CYP2E1 is not essential for either response. PMID:11032766

  9. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions

    PubMed Central

    Cavalcanti-Galdino, M.K.; da Silva, J.A.; Mendes, L.C.; dos Santos, N.A.; Simas, M.L.B.

    2014-01-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions. PMID:24676473

  10. Amanitin toxicosis in two cats with acute hepatic and renal failure.

    PubMed

    Tokarz, D; Poppenga, R; Kaae, J; Filigenzi, M; Lowenstine, L J; Pesavento, P

    2012-11-01

    Amanitin is a toxic cyclopeptide present in several species of poisonous mushrooms. Amanitin toxicosis was diagnosed in 2 cats from separate premises. Both cats initially had lethargy and vomiting, and they rapidly developed depression and neurological signs over 24-48 hours. Marked elevation of alanine aminotransferase was the primary finding, with subsequent serum chemistry values compatible with hepatic and renal failure. Histopathological findings consisted of submassive to massive acute hepatic necrosis, renal proximal tubular epithelial necrosis, and foci of necrosis and inflammation in the gastrointestinal tract. Amanitin exposure was confirmed postmortem by detection of α-amanitin in the kidney by liquid chromatography-mass spectrometry. A similar clinical course and pathological changes are reported in human and canine amanitin intoxication; however, gastrointestinal lesions are not typically described. PMID:22184185

  11. Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog.

    PubMed

    Machida, Keigo; Tsukamoto, Hidekazu; Mkrtchyan, Hasmik; Duan, Lewei; Dynnyk, Alla; Liu, Helene Minyi; Asahina, Kinji; Govindarajan, Sugantha; Ray, Ratna; Ou, Jing-Hsiung James; Seki, Ekihiro; Deshaies, Raymond; Miyake, Kensuke; Lai, Michael M-C

    2009-02-01

    Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol. PMID:19171902

  12. The microbiota regulates susceptibility to Fas-mediated acute hepatic injury.

    PubMed

    Celaj, Stela; Gleeson, Michael W; Deng, Jie; O'Toole, George A; Hampton, Thomas H; Toft, Martin F; Morrison, Hilary G; Sogin, Mitchell L; Putra, Juan; Suriawinata, Arief A; Gorham, James D

    2014-09-01

    Whereas a significant role for intestinal microbiota in affecting the pathogenesis and progression of chronic hepatic diseases is well documented, the contribution of the intestinal flora to acute liver injury has not been extensively addressed. Elucidating the influence of the intestinal microbiota on acute liver inflammation would be important for better understanding the transition from acute injury to chronic liver disease. Using the Concanavalin A (ConA)-induced liver injury model in laboratory mice, we show that the severity of acute hepatic damage varies greatly among genetically identical mice raised in different environments and harboring distinct microbiota. Through reconstitution of germ-free (GF) mice, and the co-housing of conventional mice, we provide direct evidence that manipulation of the intestinal flora alters susceptibility to ConA-induced liver injury. Through deep sequencing of the fecal microbiome, we observe that the relative abundance of Ruminococcaceae, a Gram(+) family within the class Clostridia, but distinct from segmented filamentous bacteria, is positively associated with the degree of liver damage. Searching for the underlying mechanism(s) that regulate susceptibility to ConA, we provide evidence that the extent of liver injury following triggering of the death receptor Fas varies greatly as a function of the microbiota. We demonstrate that the extent of Fas-induced liver injury increases in GF mice after microbiota reconstitution, and decreases in conventionally raised mice following reduction in intestinal bacterial load, by antibiotic treatment. We also show that the regulation of sensitivity to Fas-induced liver injury is dependent upon the toll-like receptor signaling molecule MyD88. In conclusion, the status and composition of the intestinal microbiota determine the susceptibility to ConA-induced acute liver injury. The microbiota acts as a rheostat, actively modulating the extent of liver damage in response to Fas triggering. PMID:25068658

  13. The microbiota regulates susceptibility to Fas-mediated acute hepatic injury

    PubMed Central

    Celaj, Stela; Gleeson, Michael W.; Deng, Jie; O'Toole, George A.; Hampton, Thomas H.; Toft, Martin F.; Morrison, Hilary G.; Sogin, Mitchell L.; Putra, Juan; Suriawinata, Arief A.; Gorham, James D.

    2014-01-01

    Whereas a significant role for intestinal microbiota in affecting the pathogenesis and progression of chronic hepatic diseases is well documented, the contribution of the intestinal flora to acute liver injury has not been extensively addressed. Elucidating the influence of the intestinal microbiota on acute liver inflammation would be important for better understanding the transition from acute injury to chronic liver disease. Using the Concanavalin A (ConA)-induced liver injury model in laboratory mice, we show that the severity of acute hepatic damage varies greatly among genetically identical mice raised in different environments and harboring distinct microbiota. Through reconstitution of germ-free (GF) mice, and the co-housing of conventional mice, we provide direct evidence that manipulation of the intestinal flora alters susceptibility to ConA-induced liver injury. Through deep sequencing of the fecal microbiome, we observe that the relative abundance of Ruminococcaceae, a Gram(+) family within the class Clostridia, but distinct from segmented filamentous bacteria, is positively associated with the degree of liver damage. Searching for the underlying mechanism(s) that regulate susceptibility to ConA, we provide evidence that the extent of liver injury following triggering of the death receptor Fas varies greatly as a function of the microbiota. We demonstrate that the extent of Fas induced liver injury increases in GF mice after microbiota reconstitution, and decreases in conventionally raised mice following reduction of intestinal bacterial load, by antibiotic treatment. We also show that the regulation of sensitivity to Fas induced liver injury is dependent upon the Toll-Like Receptor signaling molecule MyD88. Conclusion The status and composition of the intestinal microbiota determine the susceptibility to ConA-induced acute liver injury. The microbiota acts as a rheostat, actively modulating the extent of liver damage in response to Fas triggering. PMID:25068658

  14. Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A

    PubMed Central

    Cho, Hyosun; Kang, Hyojeung; Kim, Chang Wook; Kim, Hee Yeon; Jang, Jeong Won; Yoon, Seung Kew; Lee, Chang Don

    2016-01-01

    Background/Aims 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). Methods 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. Results 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, p<0.05; CTLA-4: 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. Conclusions Our findings are consistent with a viral-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. PMID:26347518

  15. Kudzu Extract Treatment Does Not Increase the Intoxicating Effects of Acute Alcohol in Human Volunteers

    PubMed Central

    Penetar, David M.; MacLean, Robert R.; McNeil, Jane F.; Lukas, Scott E.

    2010-01-01

    Background Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but one possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol’s effects and thus delay the desire for subsequent drinks. The present study was designed to test this hypothesis. Methods Twelve (12) healthy adult men and women (27.5±1.89 yrs old) who consumed moderate amounts of alcohol (7.8±0.63 drinks/week) participated in a double-blind, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/day) or matched placebo for nine days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. Results Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants’ subjective responses to the alcohol challenge or to alcohol’s effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. Conclusions These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences and further, the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol’s subjective or psychomotor effects. PMID:21244439

  16. Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study

    PubMed Central

    Ganne-Carrie, N; Christidis, C; Chastang, C; Ziol, M; Chapel, F; Imbert-Bismut, F; Trinchet, J; Guettier, C; Beaugrand, M

    2000-01-01

    BACKGROUND/AIMSA study was undertaken of liver biopsy samples from 229consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma.?METHODSHepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed.?RESULTS130 patients had detectable iron at enrolment. During follow up (57(28) months), 95patients died and 39patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p=0.007) by the log rank test but not in patients with hepatitis C virus related (p=0.71) or mixed (p=0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p=0.009; relative risk=2.27; 95% confidence interval 1.2to 4.19) or the continuous values (p=0.002).?CONCLUSIONSThese results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.???Keywords: cirrhosis; liver; iron; survival; hepatocellular carcinoma; alcohol PMID:10644325

  17. Acute thermogenic effects of nicotine and alcohol in healthy male and female smokers.

    PubMed

    Perkins, K A; Sexton, J E; DiMarco, A

    1996-07-01

    Nicotine intake is associated with lower body weight in both women and men. Despite its energy content, alcohol consumption is also associated with lower body weight in women but not in men. Each drug may reduce weight by acutely increasing thermogenesis. During four sessions, nicotine (20 micrograms/kg per dosing) or placebo was given to male and female smokers (n = 9 each) via measured-dose nasal spray every 30 min for 2 h after consumption of diet tonic water with or without alcohol (0.5 g/kg). Each nicotine/placebo dosing was followed by assessment of energy expenditure by indirect calorimetry. Alcohol alone induced no significant effect in men or women, whereas nicotine alone and combined with alcohol induced a significant thermogenic effect in men but not women. These results are consistent with other research suggesting a reduced thermogenic responsiveness to drugs in women and indicate that nicotine must act via appetite suppression to reduce body weight in women. Similarly, these findings do not support the notion that alcohol is inversely related to body weight in women because of excessive acute thermogenesis. PMID:8804681

  18. Fatal acute alcohol intoxication in an ALDH2 heterozygote: a case report.

    PubMed

    Yamamoto, H; Tanegashima, A; Hosoe, H; Fukunaga, T

    2000-08-14

    On an evening in November, a 25-year-old man was found dead in his bedroom. There were many empty snap-out sheets for flunitrazepam tablets in the trash at his bedside. He had been beaten by a gang of young people earlier in the morning of the same day. At the medico-legal autopsy, although there were many bruises and/or abrasions on the whole body, only slight subdural hemorrhage was observed, and none of them was thought to be the cause of death. Flunitrazepam and its metabolites were not detected in his body fluid by gas chromatography-mass spectrometry (GC-MS). Marked lung edema and a severe congestion of organs were observed. His blood alcohol concentration from the femoral vein was 2.00 mg/ml. Fatal cases of acute alcohol intoxication usually have shown higher alcohol concentration (2.25-6.23 mg/ml). Although the genotype of aldehyde dehydrogenase 2 (ALDH2) has not previously been mentioned as a contributing factor in determining the cause of death, in this case the genotype of ALDH2 was ALDH2*1/2 and thus is important. Those who possess the ALDH2*2 gene show high concentrations of acetaldehyde (AcH) at even comparatively lower alcohol levels. Consequently, the cause of death was considered to be acute alcohol intoxication including AcH poisoning. PMID:10940605

  19. The effects of acute alcohol consumption on recovery from a simulated rugby match.

    PubMed

    Barnes, Matthew J; Mundel, Toby; Stannard, Stephen R

    2012-01-01

    In this study, we investigated the effects of acute post-exercise alcohol consumption on measures of physical performance, creatine kinase, and immunoendocrine function in the 48 h following a rugby game simulation. Ten male senior rugby union players completed a rugby game simulation after which they consumed either 1 g of alcohol per kilogram of body mass or a non-alcoholic control beverage. Agility, 15 m sprint, countermovement jump, and srummaging performance were assessed pre-simulation and 24 and 48 h post-simulation. White blood cell count, testosterone, cortisol, and creatine kinase were measured before the simulation and 30 min, 12, 24, 36, and 48 h after the simulation. One week after the first trial, participants completed the second simulation after which the other beverage was consumed. The acute consumption of alcohol after a rugby game simulation negatively affected countermovement jump performance in the days following the simulation (P = 0.028). No differences between treatments were observed for the other criterion measures made in this study. In conclusion, after 80 min of a simulated rugby game, the consumption of 1 g of alcohol per kg body mass negatively impacts lower body vertical power output. However, performance of tasks requiring repeated maximal muscular effort is not affected. PMID:22168345

  20. Influence of the acute alcoholism on the phagocytic function of the mononuclear phagocytic system

    PubMed Central

    Sabino, KR; Petroianu, A; Alberti, LR

    2011-01-01

    Rationale:Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. Objective: The purpose of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. Methods and Results: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) – control, and Group 2 (n = 8) – animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with ⁸⁸mTc was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. A gamma camera was used to measure the radioactivity of these organs and of a blood clot. No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic intake, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood of both groups. Discussion: According to the experiential conditions of this work, acute ingestion of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice. PMID:22514578

  1. Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors.

    PubMed

    Li, Li; Thompson, Patricia A; Kitchens, Richard L

    2008-08-01

    Apolipoprotein E (apoE) plays important roles in lipid homeostasis, anti-inflammation, and host defense. Since tissue apoE mRNA levels have been reported to decrease during inflammatory responses, we were surprised to find that plasma apoE levels were significantly elevated during septic infections in both humans and mice. This apparent paradox was also observed during lipopolysaccharide-induced acute inflammation in mice: plasma levels of apoE increased up to 4-fold despite sharply decreased apoE gene expression in the liver, macrophages, and extrahepatic tissues. We hypothesized that apoE levels were augmented by decreased plasma clearance. Our analysis revealed that apoE associated principally with HDL in mice and that apoE was cleared from the circulation principally via LDL receptors. The acute inflammatory response decreased LDL receptor expression in the liver and significantly reduced the rate of apoE clearance. In contrast, the same inflammatory stimuli increased LDL receptor expression in macrophages. Our results define a novel acute phase mechanism that increases circulating apoE levels as apoE production decreases. Diminished hepatic LDL receptor expression may thus cooperate with elevated LDL receptor expression in macrophages to facilitate the forward transport of apoE and its associated lipids to these key defense cells. PMID:18497424

  2. The role of fat and alcohol in acute pancreatitis: A dangerous liaison.

    PubMed

    Criddle, David N

    2015-07-01

    Excessive alcohol consumption is a major trigger for severe acute pancreatitis which may lead to multi-organ dysfunction and premature death of the individual. Hyperlipidaemia is a risk factor for both acute and chronic pancreatitis and the role of fatty acids in mediating damage has received increasing attention in recent years. In the pancreas ethanol is metabolised by both oxidative and non-oxidative pathways. The latter, predominant route generates fatty acid ethyl esters (FAEEs) from fatty acid substrates via the action of diverse enzymes called FAEE synthases, including carboxylester lipase an enzyme synthesized and secreted by the acinar cells. Inhibition of the oxidative pathway promotes formation of FAEEs which induce sustained elevations of cytosolic calcium leading to inhibition of mitochondrial function, loss of ATP and necrosis of isolated pancreatic acinar cells. Furthermore, FAEEs undergo hydrolysis in the mitochondria releasing free fatty acids that exert toxic effects. Our recent work has shown that pharmacological inhibition of carboxylester lipase ameliorated detrimental effects of non-oxidative ethanol metabolism in isolated pancreatic acinar cells in vitro and in a new in vivo experimental model of alcoholic acute pancreatitis, revealing a specific enzyme target for ethanol-induced injury. Strategies that prevent FAEE synthesis, protect mitochondria, reduce calcium overload or sustain calcium homeostasis by ATP provision may provide promising therapeutic avenues for the treatment of alcoholic acute pancreatitis. PMID:25845855

  3. Behavioral economic analysis of stress effects on acute motivation for alcohol.

    PubMed

    Owens, Max M; Ray, Lara A; MacKillop, James

    2015-01-01

    Due to issues of definition and measurement, the heavy emphasis on subjective craving in the measurement of acute motivation for alcohol and other drugs remains controversial. Behavioral economic approaches have increasingly been applied to better understand acute drug motivation, particularly using demand curve modeling via purchase tasks to characterize the perceived reinforcing value of the drug. This approach has focused on using putatively more objective indices of motivation, such as units of consumption, monetary expenditure, and price sensitivity. To extend this line of research, the current study used an alcohol purchase task to determine if, compared to a neutral induction, a personalized stress induction would increase alcohol demand in a sample of heavy drinkers. The stress induction significantly increased multiple measures of the reinforcing value of alcohol to the individual, including consumption at zero price (intensity), the maximum total amount of money spent on alcohol (Omax), the first price where consumption was reduced to zero (breakpoint), and the general responsiveness of consumption to increases in price (elasticity). These measures correlated only modestly with craving and mood. Self-reported income was largely unrelated to demand but moderated the influence of stress on Omax. Moderation based on CRH-BP genotype (rs10055255) was present for Omax, with T allele homozygotes exhibiting more pronounced increases in response to stress. These results provide further support for a behavioral economic approach to measuring acute drug motivation. The findings also highlight the potential relevance of income and genetic factors in understanding state effects on the perceived reinforcing value of alcohol. PMID:25413719

  4. A case of thyroid storm complicated by acute hepatitis due to propylthiouracil treatment

    PubMed Central

    Hashim, Nazhri; Sze, Candy; Waterhouse, Mona

    2015-01-01

    Summary A 57-year-old female presented 17 days after treatment with radioactive iodine (RAI) for difficult-to-control hyperthyroidism. She was febrile, had a sinus tachycardia, and was clinically thyrotoxic. Her thyroid function tests showed a suppressed TSH <0.02 mU/l, with free thyroxine (FT4) >75 pmol/l and total triiodothyronine (TT3) 6.0 nmol/l. She was diagnosed with thyroid storm and was managed with i.v. fluids, propylthiouracil (PTU) 200 mg four times a day, prednisolone 30 mg once daily and propanolol 10 mg three times a day. She gradually improved over 2 weeks and was discharged home on PTU with β blockade. On clinic review 10 days later, it was noted that, although she was starting to feel better, she had grossly abnormal liver function (alanine transaminase (ALT) 852 U/l, bilirubin 46 μmol/l, alkaline phosphatase (ALP) 303 U/l, international normalized ratio (INR) 0.9, platelets 195×109/l). She was still mildly thyrotoxic (TSH <0.02 mU/l, FT4 31 pmol/l, TT3 1.3 nmol/l). She was diagnosed with acute hepatitis secondary to treatment with PTU. Ultrasound showed mild hepatic steatosis. PTU was stopped and she was managed with fluids and prednisolone 60 mg once daily and continued β blockade. Her liver function gradually improved over 10 days (bilirubin 9 μmol/l, ALT 164 U/l, ALP 195 U/l, INR 0.9, platelets 323×109/l) with conservative management and had normalised by clinic review 3 weeks later. This case highlights the potentially fatal, but rare, complications associated with both RAI and PTU, namely, thyroid storm and acute hepatitis respectively. Learning points Thyroid storm is an important, albeit rare, endocrinological emergency.Thyroid storm following RAI treatment is extremely rare.Management is with i.v. fluids, β blockade, anti-thyroid drugs and steroids.High dose glucocorticoid steroids can block the peripheral conversion of T4 to active T3.Liver dysfunction, acute hepatitis and potential hepatic failure are significant adverse drug reactions known to occur with PTU treatment. Supervising clinicians should be vigilant for evidence of this developing and intervene accordingly.Clinicians need to be aware of possible interactions between regular paracetamol use and PTU in predisposing to liver impairment. PMID:26279851

  5. Novel Management of Acute or Secondary Biliary Liver Conditions Using Hepatically Differentiated Human Dental Pulp Cells

    PubMed Central

    Ishkitiev, Nikolay; Imai, Toshio; Tanaka, Tomoko; Fushimi, Naho; Mitev, Vanyo; Okada, Mio; Tominaga, Noriko; Ono, Sachie; Ishikawa, Hiroshi

    2015-01-01

    The current definitive treatment for acute or chronic liver condition, that is, cirrhosis, is liver transplantation from a limited number of donors, which might cause complications after donation. Hence, bone marrow stem cell transplantation has been developed, but the risk of carcinogenesis remains. We have recently developed a protocol for hepatic differentiation of CD117+ stem cells from human exfoliated deciduous teeth (SHED). In the present study, we examine whether SHED hepatically differentiated (hd) in vitro could be used to treat acute liver injury (ALI) and secondary biliary cirrhosis. The CD117+ cell fraction was magnetically separated from SHED and then differentiated into hepatocyte-like cells in vitro. The cells were transplanted into rats with either ALI or induced secondary biliary cirrhosis. Engraftment of human liver cells was determined immunohistochemically and by in situ hybridization. Recovery of liver function was examined by means of histochemical and serological tests. Livers of transplanted animals were strongly positive for human immunohistochemical factors, and in situ hybridization confirmed engraftment of human hepatocytes. The tests for recovery of liver function confirmed the presence of human hepatic markers in the animals' blood serum and lack of fibrosis and functional integration of transplanted human cells into livers. No evidence of malignancy was found. We show that in vitro hdSHED engraft morphologically and functionally into the livers of rats having acute injury or secondary biliary cirrhosis. SHED are readily accessible adult stem cells, capable of proliferating in large numbers before differentiating in vitro. This makes SHED an appropriate and safe stem cell source for regenerative medicine. PMID:25234861

  6. Hepatic and fecal metabolomic analysis of the effects of Lactobacillus rhamnosus GG on alcoholic fatty liver disease in mice.

    PubMed

    Shi, Xue; Wei, Xiaoli; Yin, Xinmin; Wang, Yuhua; Zhang, Min; Zhao, Cuiqing; Zhao, Haiyang; McClain, Craig J; Feng, Wenke; Zhang, Xiang

    2015-02-01

    The interactions among the gut, liver, and immune system play an important role in liver disease. Probiotics have been used for the treatment and prevention of many pathological conditions, including liver diseases. Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS) was used herein, in conjunction with chemometric data analysis, to identify metabolites significantly affected by probiotics in mice fed with or without alcohol. The metabolomics analysis indicates that the levels of fatty acids increased in mouse liver and decreased in mouse feces when mice were chronically exposed to alcohol. Supplementing the alcohol-fed mice with culture supernatant from Lactobacillus rhamnosus GG (LGGs) normalized these alcohol-induced abnormalities and prevented alcoholic liver disease (ALD). These results agree well with previous studies. In addition to diet-derived long chain fatty acids (LCFAs), LGGs may positively modify the gut's bacterial population to stimulate LCFA synthesis, which has been shown to enhance intestinal barrier function, reduce endotoxemia, and prevent ALD. We also found that several amino acids, including l-isoleucine, a branched chain amino acid, were downregulated in the liver and fecal samples from animals exposed to alcohol and that the levels of these amino acids were corrected by LGGs. These results demonstrate that LGGs alleviates alcohol-induced fatty liver by mechanisms involving increasing intestinal and decreasing hepatic fatty acids and increasing amino acid concentration. PMID:25592873

  7. Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment.

    PubMed

    Watson, Bianca; Conigrave, Katherine M; Wallace, Cate; Whitfield, John B; Wurst, Friedrich; Haber, Paul S

    2007-05-01

    Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test (AUDIT-C). A semi-structured interview was used in 53 subjects to assess alcohol use in detail, psychological health, discrimination and access to HCV treatment. Feasibility of brief intervention for alcohol misuse was assessed. Of the screening participants, 73% reported they were HCV positive. Of the detailed interview participants, 26% reported no drinking in the past month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking guidelines. Twenty subjects received brief intervention and among 17 re-interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003). Severe or extremely severe depression, stress and anxiety were found in 57%, 51% and 40% of interviewees respectively. Episodic heavy drinking, mental health problems, perceived discrimination, limited knowledge concerning HCV were all common and uptake of HCV treatment was poor. Brief intervention for alcohol use problems was acceptable to OMT patients, and warrants further study. PMID:17454012

  8. Post‐load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non‐alcoholic fatty liver disease

    PubMed Central

    Svegliati‐Baroni, G; Bugianesi, E; Bouserhal, T; Marini, F; Ridolfi, F; Tarsetti, F; Ancarani, F; Petrelli, E; Peruzzi, E; Cascio, M Lo; Rizzetto, M; Marchesini, G; Benedetti, A

    2007-01-01

    Background Insulin resistance is a significant risk factor for hepatic fibrosis in patients with both non‐alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), either directly or by favouring hepatic steatosis. Several methods are available to assess insulin resistance, but their impact on this issue has never been evaluated. Aims To determine the relative contribution of steatosis, metabolic abnormalities and insulin resistance, measured by different basal and post‐load parameters, to hepatic fibrosis in CHC and in NAFLD patients. Methods In 90 patients with CHC and 90 pair‐matched patients with NAFLD, the degree of basal insulin resistance (by the homeostasis model assessment, (HOMA)) and post‐load insulin sensitivity (by the oral glucose insulin sensitivity (OGIS) index) was assessed, together with the features of the metabolic syndrome according to Adult Treatment Panel III definition. Data were correlated with hepatic histopathology. Results The prevalence of basal insulin resistance (HOMA values >75th percentile of normal) was 23.3% in CHC patients and 57.8% in NAFLD, but it increased to 28.8 and 67.8% when measured by post‐load insulin resistance (OGIS <25th percentile). In a multivariate model, after adjustment for age, gender and body mass index, OGIS was a predictor of severe fibrosis in CHC and in NAFLD patients, independently of steatosis. An OGIS value below the cut‐off of the 25th percentile increased the likelihood ratio of severe fibrosis by a factor of 1.5–2 and proved to be a more sensitive and generally more specific test than HOMA‐R for the identification of subjects with severe fibrosis both in NAFLD and in CHC. Conclusions Post‐load insulin resistance (OGIS <9.8 mg/kg/min) is associated with severe hepatic fibrosis in both NAFLD and CHC patients, and may help identify subjects at risk of progressive disease. PMID:17392334

  9. Acute Viral Hepatitis E Is Associated with the Development of Myocarditis

    PubMed Central

    Rangegowda, Devraja; Vashishtha, Chitranshu; Bhatia, Vikram; Khumuckham, Jelen Singh; Kumar, Badal

    2015-01-01

    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. PMID:25802773

  10. Acute viral hepatitis e is associated with the development of myocarditis.

    PubMed

    Premkumar, M; Rangegowda, Devraja; Vashishtha, Chitranshu; Bhatia, Vikram; Khumuckham, Jelen Singh; Kumar, Badal

    2015-01-01

    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. PMID:25802773

  11. Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?

    PubMed Central

    Weigand, Kilian; Riediger, Carina; Stremmel, Wolfgang; Flechtenmacher, Christa; Encke, Jens

    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. PMID:17226914

  12. Molecular epidemiology of hepatitis B virus genotypes circulating in acute hepatitis B patients in the Campania region.

    PubMed

    Sagnelli, Caterina; Ciccozzi, Massimo; Pisaturo, Mariantonietta; Zehender, Gianguglielmo; Lo Presti, Alessandra; Alessio, Loredana; Starace, Mario; Lovero, Domenica; Sagnelli, Evangelista; Coppola, Nicola

    2014-10-01

    Fifty-three HBV-DNA-positive patients with symptomatic acute hepatitis B were enrolled from 1999 to 2010 to evaluate molecular and phylogenetic changes in HBV in southern Italy. HBV polymerase region was evaluated by direct sequencing in plasma samples obtained at first observation. Different data sets were aligned and a phylogenetic tree was inferred using PhyML program. Statistical robustness was confirmed with a bootstrap analysis. A Bayesian Markov chain Monte Carlo method and a Bayesian skyline plot were used to estimate the evolution of our samples. The dN/dS rate (ω) was estimated by the maximum likelihood approach to investigate the presence of codons under positive selection. The MacClade program was used to test viral gene out/in flow only among HBV-D3 subgenotype patients with different risk factors. Of the 53 patients, 83% were born in Italy and 17% were foreigners. HBV genotype D was prevalent (64.1%), followed by genotype A (26.4%), E (3.8%), and F (5.7%). The prevalent subgenotype was D3 (70.6%). The Bayesian tree of the 24 D3 subgenotypes showed two main clades both dated 1994; 40% of viral gene flow observed was from intravenous drugs users and heterosexual patients. Phylogenetic analysis of HBV isolates showed that HBV-D3 remains the prevalent genotype, but also subgenotype A2 has become frequent in southern Italy. This may be of clinical relevance in years to come, since patients with HBV-genotype-A chronic infection less frequently than those with genotype D develop HBeAg-negative chronic hepatitis and respond more frequently to alfa-interferon treatment. PMID:24980631

  13. Alcohol concentration determines the type of atrial arrhythmia induced in a porcine model of acute alcoholic intoxication.

    PubMed

    Anadon, M J; Almendral, J; González, P; Zaballos, M; Delcan, J L; De Guevara, J L

    1996-11-01

    Alcohol abuse has long been suspected clinically to cause paroxysmal atrial tachyarrhythmias. However, such a relationship has never been conclusively proven, partly due to the lack of experimental evidence. Although atrial fibrillation (AF) is the most common atrial arrhythmia attributed to acute alcoholic ingestion, atrial flutter has occasionally been noted. We analyzed the possible role of alcohol in initiation and/or maintenance of a variety of atrial tachyarrhythmias in a closed-chest porcine model. Nine pigs underwent nine endocardial right atrial stimulation protocols (RASP) at baseline and 17 RASPs after increasing doses of ethanol (first infusion 1,230 mg/kg, second infusion 870 mg/kg) by means of one multipolar catheter advanced under heavy sedation from the femoral vein. Each RASP included 1, 2, and 3 extrastimuli, and rapid pacing at 5 times diastolic threshold. Venous ethanol concentrations were measured (HPGC method) every 10 minutes and at the time of arrhythmia induction. Atrial tachyarrhythmias were induced in 4 of 9 baseline RASPs, and lasted for a mean of 21 seconds, and in 16 of 17 RASPs after alcohol lasting for a mean of 357 seconds. Only fibrillation was observed at the baseline RASP. The atrial tachyarrhythmias induced after alcohol were AF in 11 RASPs and atrial flutter in 5 RASPs (in 5 animals). The mean venous ethanol concentration at the time of the longest arrhythmia induced for each RASP were 200 +/- 89 mg/dL for RASP inducing fibrillation and 292 +/- 40 mg/dL for RASP inducing flutter (P < 0.05). Flutter tended to be sustained (> 1 minute in duration) more often than fibrillation (4 of 5 flutter vs 2 of 11 fibrillation P < 0.05). In three experiments, atrial flutter persisted for > 10 minutes and was terminated by overdrive atrial pacing. We concluded: (1) in this closed-chest porcine model, an ethanol infusion facilitates a variety of atrial arrhythmias related to the ethanol concentration; (2) flutter tended to be sustained, and its termination by overdrive pacing suggests the possibility of an alcohol induced reentrant mechanism; and (3) the higher concentration required for atrial flutter, exceeding that usually seen in humans, may help to explain the rarity of atrial flutter in clinical alcohol intoxication. PMID:8945078

  14. Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ahn, Jem Ma; Paik, Yong-Han; Min, Sin Yeong; Cho, Ju Yeon; Sohn, Won; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2016-01-01

    Background/Aims The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). Methods Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). Results A total of 186 patients were included: 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, p<0.001), and there was no significant difference between the NAFLD and ALD groups (ρ=0.569, p<0.001; ρ=0.519, p<0.001; p=0.635). Using CAP, area under receiver operating characteristic curves for ≥S2 and ≥S3 steatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥90%, CAP cutoffs for the detection of ≥S2 and ≥S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups. Conclusions The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD. PMID:26347511

  15. Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress.

    PubMed

    Ding, Ren-Bo; Tian, Ke; Cao, Yi-Wei; Bao, Jiao-Lin; Wang, Meng; He, Chengwei; Hu, Yuanjia; Su, Huanxing; Wan, Jian-Bo

    2015-03-11

    The aim of present study was to evaluate the effects of Panax notoginseng saponins (PNS) against acute ethanol-induced liver injury and further to elucidate its probable mechanisms. Mice were treated with PNS (100 or 300 mg/kg) once daily for seven consecutive days priors to ethanol gavage (4.7 g/kg) every 12 h for a total of three doses. Acute alcohol gavage dramatically significantly increased serum activities of alanine aminotransferase (ALT) (23.4 ± 5.0 IU/L vs 11.7 ± 4.1 IU/L) and aspartate aminotransferase (AST) (52.6 ± 14.9 IU/L vs 31.1 ± 12.9 IU/L), and hepatic triglyceride level (4.04 ± 0.64 mg/g vs 1.92 ± 0.34 mg/g), these elevations were significantly diminished by pretreatment with PNS at dose of 100 mg/kg or 300 mg/kg. Alcohol exposure markedly induced the lipolysis of white adipose tissue (WAT), up-regulated protein expression of the phosphorylated hormone-sensitive lipase (p-HSL, p < 0.01), and total HSL (p < 0.01), and enhanced fatty acid uptake capacity in liver as indicated by increasing hepatic CD36 expression (p < 0.01), these effects were attenuated by PNS treatment. Additionally, PNS suppressed the elevation of reactive oxygen species (ROS) production and malondialdehyde (MDA) content, reduced TNF-α and IL-6 levels, restored glutathione (GSH) level, enhanced the superoxide dismutase (SOD) activity in liver, and abrogated cytochrome P450 2E1 (CYP2E1) induction. These data demonstrated that pretreatment with PNS protected against acute ethanol-induced liver injury, possibly through ameliorating hepatic lipid accumulation and reducing CYP2E1-mediated oxidative stress. Our findings also suggested that PNS may be potential to be developed as an effective agent for acute ethanol-induced liver injury. PMID:25665731

  16. Increased activity of the complement system in the liver of patients with alcoholic hepatitis

    PubMed Central

    Shen, Hong; French, Barbara A.; Liu, Hui; Tillman, Brittany C.; French, Samuel W.

    2014-01-01

    Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH. PMID:25217811

  17. Curcumin prevents the non-alcoholic fatty hepatitis via mitochondria protection and apoptosis reduction

    PubMed Central

    Wang, Long; lv, Yisong; Yao, Huixiang; Yin, Li; Shang, Jianhui

    2015-01-01

    Background: Non-alcoholic fatty hepatitis (NASH) is highly prevalent, mitochondria damage is the main pathophysiological characteristic of NASH. However, treatment for mitochondria damage is rarely reported. Methods: NASH model was established in rats, the protective effects of curcumin were evaluated by histological observation; structure and function assessments of mitochondria; and apoptotic genes expression. Results: NASH rats treated with curcumin displayed relatively slight liver damage when compared with NASH livers. The average mitochondrial length and width of NASH (12.0 ± 3.2 and 5.1 ± 1.1 micrometers) were significantly longer than that of normal (6.2 ± 2.1 and 2.1 ± 1.5 micrometers) and NASH treated with curcumin (7.4 ± 1.2 and 3.2 ± 1.5 micrometers) rats. The average malondialdehyde (MDA) and 4-hydroxy nonyl alcohol (HNE) levels in liver homogenates of NASH rats (4.23 ± 0.22 and 19.23 ± 2.3 nmol/Ml) were significantly higher than these in normal (1.32 ± 0.12 and 3.52 ± 0.43 nmol/mL) and NASH treated with curcumin (1.74 ± 0.11 and 4.66 ± 0.99 nmol/mL) rats. The expression levels of CytC, Casp3 and Casp8 of the NASH livers were significantly higher than normal and NASH treated with curcumin rats livers. Conclusion: Our data demonstrated that curcumin prevents the NASH by mitochondria protection and apoptosis reduction and provided a possible novel treatment for NASH. PMID:26617882

  18. Acute onset anarthria without hepatic manifestation: a rare presentation of Wilson disease

    PubMed Central

    Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S

    2013-01-01

    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. PMID:23966348

  19. Acute hepatitis C virus infection related to capillary blood glucose meter

    PubMed Central

    Inayat, Faisal; Rai, Aitzaz BinSultan

    2016-01-01

    Hepatitis C virus (HCV) infects an estimated 130-150 million people worldwide, becoming the major cause of chronic liver disease, cirrhosis, hepatocellular carcinoma, and liver transplantation. There are various preventable modes of transmission of HCV infection, including needlestick and sharps injuries. However, HCV infection secondary to needlestick injury by a capillary blood glucose meter (CBGM) lancet has not been previously well reported. We describe an unusual case of a 25-year-old male medical student, acquiring acute HCV infection with a lancing device of CBGM. The source patient was a 54-year-old diabetic male with positive anti-HCV test results. In our patient, after 3 months of initial exposure, a standard set of investigations confirmed the diagnosis of acute HCV infection with the same genotype (3a) as the source. The CBGM, as in our case, may have a role in the transmission of HCV infection warranting radical advancements in diabetes screening and monitoring technology. PMID:26739982

  20. [Anesthesia for a patient with a giant hepatoma associated with severe acute hepatic damage].

    PubMed

    Tanaka, M; Tanaka, Y

    1991-07-01

    We gave anesthesia to a patient for extensive right lobe hepatectomy. Although the liver function test revealed acute exacerbation just before the operation, we carried out anesthesia, diagnosing it to be due to giant liver tumor. The anesthesia was maintained with nitrous oxide, oxygen and epidural anesthesia with 1.5% lidocaine or 0.25% bupivacaine. A biopump inserted between the inferior vena cava and the left basilic vein was used during the right lobe resection to maintain sufficient venous return to the right atrium during the right lobe resection. Ketone body ratio was checked frequently in order to know the remnant liver energy charge and glucose was loaded properly. The surgery and anesthesia were uneventful. The resected right lobe weighed 2380 g, with necrosis of moderate size at the posterior-inferior segment. The serum transaminase decreased markedly after operation. It is important to have accurate diagnosis before we anesthetize patients with acute hepatic damage. PMID:1656114

  1. Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats

    PubMed Central

    Chen, Ya-Ling; Peng, Hsiang-Chi; Wang, Xiang-Dong

    2015-01-01

    Background In this study, we evaluated the influence of an ethanol-containing diet with high saturated fatty acids (SFAs) on alcoholic liver disease (ALD) in rats. Methods Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fed an ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control (C) group pair-fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed an ethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat (CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat. Results After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST) activities in E and EHS groups were significantly higher than those of C group. Significantly higher scores of inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores of necrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasma adiponectin concentrations were observed in both E and EHS groups, compared to C group, plasma adiponectin in EHS group was significantly higher than that in E group. There was no change in hepatic peroxisome proliferator activated receptor (PPAR)-? expression between E and C groups, and rats in EHS group showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasma TGF-?1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidized glutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in E and EHS groups; however, there was no significant difference between E and EHS groups. Significantly increased hepatic CYP2E1 expression was observed in both E and EHS groups, while at the same time, hepatic CYP2E1 in EHS group was the highest among all groups. The hepatic tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6, and IL-10 concentrations in the E group were significantly higher than those in C group, whereas the hepatic IL-6 and IL-10 concentrations in ES group were significantly lower than those of E group. Conclusions These results suggested that dietary saturated fats may inhibit hepatic fat accumulation and induce hepatic fibrosis in rats under chronic alcohol intake. PMID:26151057

  2. Acute Increase in Hepatic Arterial Flow During TIPS Identified by Intravascular Flow Measurements

    SciTech Connect

    Radeleff, Boris Sommer, Christof-Matthias; Heye, Tobias; Lopez-Benitez, Ruben; Sauer, Peter; Schmidt, Jan; Kauczor, Haus-Ulrich; Richter, Goetz Martin

    2009-01-15

    The purpose of this study was to investigate alterations of hepatic arterial flow during transjugular intrahepatic portosystemic stent shunt (TIPS) applying intravascular Doppler sonography. This prospective monocenter study included 25 patients with liver cirrhosis (alcohol induced [n = 19], chronic hepatitis associated [n = 3], primary biliary cirrhosis associated [n = 1], and cryptogenic [n = 2]) successfully treated with TIPS. All patients underwent intravascular hepatic arterial flow measurements during TIPS using an endoluminal flow sensor. The average arterial peak velocity (APV) and the maximum arterial peak velocity (MPV) were registered. Twenty-two patients (88%) showed increased APV, one patient (4%) showed unaffected APV, and two patients (8%) showed decreased APV after TIPS. The average portosystemic pressure gradient decreased significantly, from 22.0 {+-} 5.1 mmHg before TIPS to 11.0 {+-} 4.1 mmHg after TIPS (-50.0%; p < 0.0001). The average APV increased significantly, from 41.9 {+-} 17.8 cm/s before TIPS to 60.7 {+-} 19.0 cm/s after TIPS (+44.9%; p < 0.0001). The average MPV increased significantly, from 90.8 {+-} 31.7 cm/s before TIPS to 112.6 {+-} 34.9 cm/s after TIPS (+24.0%; p = 0.0002). These changes in perfusion set in within seconds after TIPS tract formation in all the patients with increased APV. We conclude that TIPS-induced portosystemic decompression leads to a significant increase in hepatic arterial flow. The changes occurred within seconds, suggesting a reflex-like mechanism.

  3. Stereotypic behavioral response of rat fetuses to acute hypoxia is altered by maternal alcohol consumption.

    PubMed

    Smotherman, W P; Robinson, S R

    1987-10-01

    Transient compression of the umbilical cord has been implicated as a potential cause of unexplained brain damage and/or fetal death. We induced acute fetal hypoxia by compressing the umbilical cord of the fetal rat with a microvascular clamp. Direct observation of fetal behavior immediately after cord compression identified a three-phase behavioral response to acute hypoxia, consisting of an initial suppression in motor activity, a brief period of hyperactivity, and a secondary suppression of movement. All three phases occurred in less than 2 minutes from the onset of hypoxia. The stereotypic hypoxic response of rat fetuses may be adaptive as a means of removing mechanical sources of umbilical cord compression. Among fetuses exposed to alcohol in utero, the response to hypoxia was diminished in intensity and duration. Because of their altered hypoxic response, alcohol-exposed fetuses may therefore be at greater risk from transient cord compression in utero. PMID:3674174

  4. Prolonged nosocomial outbreak of hepatitis A arising from an alcoholic with pneumonia.

    PubMed

    Jensenius, M; Ringertz, S H; Berild, D; Bell, H; Espinoza, R; Grinde, B

    1998-01-01

    From April to June 1996, an outbreak of hepatitis A virus (HAV) infection affecting 15 nurses, patients and household contacts occurred in the Department of Internal Medicine at Aker University Hospital, Oslo. The index case was a homeless alcoholic who was hospitalized in March 1996 with pneumonia while simultaneously incubating HAV infection. Four secondary cases were infected by the index case, while another 10 cases were caused by a continuous spread of infection within the department during the following months. Sequence of the VP1/P2A junction of HAV was obtained from 9 patients, including the index case, and all sequences were identical to each other. Mass vaccination of hospital employees with a formalin-inactivated HAV-vaccine took place in late May, and following this the outbreak stopped. Several factors probably combined to account for this unusual outbreak, e.g. an index case unsuspected of incubating with HAV infection, and a low prevalence rate of protective antibodies to HAV among the hospital staff. PMID:9730295

  5. Epigenetic signatures of alcohol abuse and hepatitis infection during human hepatocarcinogenesis

    PubMed Central

    Hlady, Ryan A.; Tiedemann, Rochelle L.; Puszyk, William; Zendejas, Ivan; Roberts, Lewis R.; Choi, Jeong-Hyeon; Liu, Chen; Robertson, Keith D.

    2014-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Deregulated DNA methylation landscapes are ubiquitous in human cancers. Interpretation of epigenetic aberrations in HCC is confounded by multiple etiologic drivers and underlying cirrhosis. We globally profiled the DNA methylome of 34 normal and 122 liver disease tissues arising in settings of hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each exposure leaves unique and overlapping signatures on the methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatocarcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil conserved epigenetic signatures in HCC. Taken together, this study reveals profound epigenome deregulation in HCC beginning during cirrhosis and influenced by common environmental agents. These results lay the foundation for defining epigenetic drivers and clinically useful methylation markers for HCC. PMID:25294808

  6. Mass spectrometry characterization of circulating human serum albumin microheterogeneity in patients with alcoholic hepatitis.

    PubMed

    Naldi, Marina; Baldassarre, Maurizio; Domenicali, Marco; Giannone, Ferdinando Antonino; Bossi, Matteo; Montomoli, Jonathan; Sandahl, Thomas Damgaard; Glavind, Emilie; Vilstrup, Hendrik; Caraceni, Paolo; Bertucci, Carlo

    2016-04-15

    Human serum albumin (HSA) is the most abundant plasma protein, endowed with several biological properties unrelated to its oncotic power, such as antioxidant and free-radicals scavenging activities, binding and transport of many endogenous and exogenous substances, and regulation of endothelial function and inflammatory response. These non-oncotic activities are closely connected to the peculiarly dynamic structure of the albumin molecule. HSA undergoes spontaneous structural modifications, mainly by reaction with oxidants and saccharides; however, patients with cirrhosis show extensive post-transcriptional changes at several molecular sites of HSA, the degree of which parallels the severity of the disease. The present work reports the development and application of an innovative LC-MS analytical method for a rapid and reproducible determination of the relative abundance of HSA isoforms in plasma samples from alcoholic hepatitis (AH) patients. A condition of severe oxidative stress, similar to that observed in AH patients, is associated with profound changes in circulating HSA microheterogeneity. More interestingly, the high resolution provided by the analytical platform allowed the monitoring of novel oxidative products of HSA never reported before. PMID:26852162

  7. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats

    PubMed Central

    2011-01-01

    Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats. PMID:21569626

  8. The Protective Effect of Resveratrol on Concanavalin-A-Induced Acute Hepatic Injury in Mice

    PubMed Central

    Zhou, Yingqun; Chen, Kan; He, Lei; Xia, Yujing; Dai, Weiqi; Wang, Fan; Li, Jingjing; Li, Sainan; Liu, Tong; Wang, Jianrong; Lu, Wenxia; Yin, Qin; Zhou, Yuqing; Lu, Jie; Teng, Hongfei; Guo, Chuanyong

    2015-01-01

    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-? 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-?, 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. PMID:26089871

  9. Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis

    PubMed Central

    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. PMID:27031695

  10. The role of chemokines in acute and chronic hepatitis C infection

    PubMed Central

    Fahey, Stephen; Dempsey, Eugene; Long, Aideen

    2014-01-01

    Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine. PMID:23954947

  11. Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

    PubMed

    Asher, Alice; Lum, Paula J; Page, Kimberly

    2012-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

  12. Assessing Candidacy for Acute Hepatitis C Treatment Among Active Young Injection Drug Users: A Case-Series Report

    PubMed Central

    Asher, Alice; Lum, Paula J.; Page, Kimberly

    2011-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All 5 acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. . Establishing treatment candidacy for young IDU in the acute phase involves various health domains. Acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

  13. Gene expression analysis during acute hepatitis C virus infection associates dendritic cell activation with viral clearance.

    PubMed

    Zabaleta, Aintzane; Riezu-Boj, Jose-Ignacio; Larrea, Esther; Villanueva, Lorea; Lasarte, Juan Jose; Guruceaga, Elizabeth; Fisicaro, Paola; Ezzikouri, Sayeh; Missale, Gabriele; Ferrari, Carlo; Benjelloun, Soumaya; Prieto, Jesús; Sarobe, Pablo

    2016-05-01

    Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses, gene expression was analyzed in DC from patients during acute HCV infection. By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from patients who become chronically infected (ANR), as well as in healthy individuals (CTRL) and chronically-infected patients (CHR). For pDC, a high number of upregulated genes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Divergent behavior of ANR was also observed when analyzing DC from CTRL and CHR, with ANR patients clustering again apart from these groups. These differences corresponded to metabolism-associated genes and genes belonging to pathways relevant for DC activation and cytokine responses. Thus, upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection. J. Med. Virol. 88:843-851, 2016. © 2015 Wiley Periodicals, Inc. PMID:26447929

  14. Acute and residual interactive effects of repeated administrations of oral methamphetamine and alcohol in humans

    PubMed Central

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.

    2011-01-01

    Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance, and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed this 20-day within-participant, residential laboratory study. During four 5-day blocks of sessions, participants were administered oral methamphetamine (0, 10 mg) combined with alcohol (0, 0.375, 0.75 g/kg) three times (day 2: AM, day 2: PM, and day 3: PM). Breath alcohol concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and repeatedly thereafter. Subjective and objective sleep measures were also assessed; residual effects were assessed on days 3–5 of each block. Following the first drug administration, the methamphetamine–alcohol combination produced greater elevations of heart rate and ratings of “good drug effect” compared to either drug alone. Methamphetamine attenuated alcohol-related performance decrements and feelings of intoxication, whereas alcohol attenuated methamphetamine-related sleep disruptions. By the third administration, many of these effects were significantly diminished, suggesting that participants developed tolerance. Few residual effects were observed. These data show that methamphetamine combined with alcohol produced a profile of effects that was different from the effects of either drug alone. The largely positive effects of the drug combination (i.e., greater euphoria, and fewer performance and sleep disruptions) might explain why these drugs are often used in combination. PMID:21748253

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

    PubMed Central

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

    2015-01-01

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

  16. Atg7 Knockdown Augments Concanavalin A-Induced Acute Hepatitis through an ROS-Mediated p38/MAPK Pathway

    PubMed Central

    Li, Xuefeng; Xie, Qing; Wu, Min

    2016-01-01

    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. PMID:26939081

  17. Alcoholic liver disease

    PubMed Central

    Bruha, Radan; Dvorak, Karel; Petrtyl, Jaromir

    2012-01-01

    Alcohol use disorders affect millions of individuals worldwide. Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs. Alcoholic liver disease (ALD) may take the form of acute involvement (alcoholic hepatitis) or chronic liver disease (steatosis, steatohepatitis, fibrosis and cirrhosis). The severity and prognosis of alcohol-induced liver disease depends on the amount, pattern and duration of alcohol consumption, as well as on the presence of liver inflammation, diet, nutritional status and genetic predisposition of an individual. While steatosis is an almost completely benign disease, liver cirrhosis is associated with marked morbidity, mortality and life expectancy shortening. The median survival of patients with advanced cirrhosis is 1-2 years. Severe acute alcoholic hepatitis (AH) is associated with mortality as high as 50%. It has been managed with corticoids, pentoxifylline and enteral nutrition, although evidence based data are still conflicting. Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH. Absolute abstinence is a basic condition for any treatment of acute or chronic ALD, the other therapeutical procedure being of a supportive nature and questionable significance. Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alcohol dependent patients. Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation, which leads to a markedly prolonged life expectancy. The crucial step in ALD prevention is in the prevention of alcohol abuse, whereas the prevention of liver injury in active alcohol abusers is not clinically applicable. PMID:22489260

  18. A Herbal Composition of Semen Hoveniae, Radix Puerariae, and Fructus Schisandrae Shows Potent Protective Effects on Acute Alcoholic Intoxication in Rodent Models

    PubMed Central

    Xiong, Jie; Guo, Yu; Li, Lu-yi; Hu, Hang; Qu, Xin-lan; Sun, Xi-zhen; Liu, Sheng-hua; Wang, Hui

    2012-01-01

    This study is designed to evaluate the effects of a herbal composition of Semen Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF) against acute alcoholic intoxication. The animals were treated with SRF extract (SRFE) for 14 days, and ethanol was conducted subsequent to the final treatment. The effects of SRFE on righting reflex, inebriety rates, kinetic parameters of blood ethanol and acetaldehyde were determined. In addition; levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the activities of cytochrome P450 2E1 (CYP2E1), selected antioxidative enzymes, and the contents of malonaldehyde (MDA) were measured. SRFE-pretreated rodents exhibited lower rates of intoxication, longer times to loss of righting reflex, and shortened times to recovery of righting reflex than in controls. The peak concentrations and area under the time-concentration curves were lower in the pretreated animals than in controls, which corresponded to higher levels of ADH and ALDH in both gastrointestines and livers of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE-pretreated animals, which also exhibited higher activities of some antioxidant enzymes and lower hepatic MDA levels. These findings suggest that the anti-inebriation effects of SRFE may involve inhibition of ethanol absorption, promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions. PMID:23118795

  19. Acute intermittent porphyria causes hepatic mitochondrial energetic failure in a mouse model.

    PubMed

    Homedan, Chadi; Laafi, Jihane; Schmitt, Caroline; Gueguen, Naïg; Lefebvre, Thibaud; Karim, Zoubida; Desquiret-Dumas, Valérie; Wetterwald, Céline; Deybach, Jean-Charles; Gouya, Laurent; Puy, Hervé; Reynier, Pascal; Malthièry, Yves

    2014-06-01

    Acute intermittent porphyria (AIP), an inherited hepatic disorder, is due to a defect of hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP is characterized by recurrent, life-threatening attacks at least partly due to the increased hepatic production of 5-aminolaevulinic acid (ALA). Both the mitochondrial enzyme, ALA synthase (ALAS) 1, involved in the first step of heme biosynthesis, which is closely linked to mitochondrial bioenergetic pathways, and the promise of an ALAS1 siRNA hepatic therapy in humans, led us to investigate hepatic energetic metabolism in Hmbs KO mice treated with phenobarbital. The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes I (-52%, (**)p<0.01), II (-50%, (**)p<0.01) and III (-55%, (*)p<0.05), and decreased activity of α-ketoglutarate dehydrogenase (-64%, (*)p<0.05), citrate synthase (-48%, (**)p<0.01) and succinate dehydrogenase (-53%, (*)p<0.05). Complex II-driven succinate respiration was also significantly affected. Most of these metabolic alterations were at least partially restored after the phenobarbital arrest and heme arginate administration. These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC. This profound and reversible impact of AIP on mitochondrial energetic metabolism offers new insights into the beneficial effect of heme, glucose and ALAS1 siRNA treatments by limiting the cataplerosis of TCA cycle. PMID:24727425

  20. Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis

    PubMed Central

    Schröder, Torsten; Kucharczyk, David; Bär, Florian; Pagel, René; Derer, Stefanie; Jendrek, Sebastian Torben; Sünderhauf, Annika; Brethack, Ann-Kathrin; Hirose, Misa; Möller, Steffen; Künstner, Axel; Bischof, Julia; Weyers, Imke; Heeren, Jörg; Koczan, Dirk; Schmid, Sebastian Michael; Divanovic, Senad; Giles, Daniel Aaron; Adamski, Jerzy; Fellermann, Klaus; Lehnert, Hendrik; Köhl, Jörg; Ibrahim, Saleh; Sina, Christian

    2016-01-01

    Objective Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with an enhanced risk for liver and cardiovascular diseases and mortality. NAFLD can progress from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH). However, the mechanisms predisposing to this progression remain undefined. Notably, hepatic mitochondrial dysfunction is a common finding in patients with NASH. Due to a lack of appropriate experimental animal models, it has not been evaluated whether this mitochondrial dysfunction plays a causative role for the development of NASH. Methods To determine the effect of a well-defined mitochondrial dysfunction on liver physiology at baseline and during dietary challenge, C57BL/6J-mtFVB/N mice were employed. This conplastic inbred strain has been previously reported to exhibit decreased mitochondrial respiration likely linked to a non-synonymous gene variation (nt7778 G/T) of the mitochondrial ATP synthase protein 8 (mt-ATP8). Results At baseline conditions, C57BL/6J-mtFVB/N mice displayed hepatic mitochondrial dysfunction characterized by decreased ATP production and increased formation of reactive oxygen species (ROS). Moreover, genes affecting lipid metabolism were differentially expressed, hepatic triglyceride and cholesterol levels were changed in these animals, and various acyl-carnitines were altered, pointing towards an impaired mitochondrial carnitine shuttle. However, over a period of twelve months, no spontaneous hepatic steatosis or inflammation was observed. On the other hand, upon dietary challenge with either a methionine and choline deficient diet or a western-style diet, C57BL/6J-mtFVB/N mice developed aggravated steatohepatitis as characterized by lipid accumulation, ballooning of hepatocytes and infiltration of immune cells. Conclusions We observed distinct metabolic alterations in mice with a mitochondrial polymorphism associated hepatic mitochondrial dysfunction. However, a second hit, such as dietary stress, was required to cause hepatic steatosis and inflammation. This study suggests a causative role of hepatic mitochondrial dysfunction in the development of experimental NASH. PMID:27069868

  1. Acute multiple focal neuropathies and delayed postanoxic encephalopathy after alcohol intoxication

    PubMed Central

    Wang, Wei-Che; Yang, Hsiu-Chun; Chen, Yao-Jen

    2015-01-01

    Acute-onset alcohol-associated neuropathy is only occasionally reported, and delayed postanoxic encephalopathy is rare. Here, we report a male who developed acute multiple focal neuropathies and later delayed postanoxic encephalopathy after alcohol intoxication. He had hypoxia and rhabdomyolysis, presenting with acute renal failure initially, and cardiopulmonary support, including mechanical ventilation, led to improvement of the patient at the acute stage. He suffered from bilateral hand numbness and mild weakness of the right lower limb thereafter. Nerve-conduction study revealed no pickup of compound muscle action potential or sensory nerve action potential in the bilateral ulnar nerve, but showed attenuated amplitude of compound muscle action potential in the right femoral nerve. Multiple focal neuropathies were suspected, and he received outpatient rehabilitation after being discharged. However, the patient developed gradual onset of weakness in four limbs and cognitive impairment 23 days after the hypoxia event. Brain computed tomography showed low attenuation over bilateral globus pallidus, and brain magnetic resonance imaging disclosed diffuse increased signal intensity on T2-weighted images and fluid-attenuated inversion recovery in bilateral white matter. He was admitted again under the impression of delayed postanoxic brain injury. Supportive treatment and active rehabilitation were given. He had gradual improvement in motor and functional status after rehabilitation. He could walk with festinating gait under supervision, and needed only minimal assistance in performing activities of daily living approximately 1 year later. PMID:26229472

  2. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  3. Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging

    PubMed Central

    Bopp, A; Wartlick, F; Henninger, C; Kaina, B; Fritz, G

    2013-01-01

    To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (γH2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGFβ, αSMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the γH2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGFβ, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging. PMID:23519127

  4. Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging.

    PubMed

    Bopp, A; Wartlick, F; Henninger, C; Kaina, B; Fritz, G

    2013-01-01

    To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (γH2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGFβ, αSMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the γH2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGFβ, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging. PMID:23519127

  5. Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E

    MedlinePlus

    ... 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 ...

  6. Hospital-based, acute care encounters after radiofrequency ablation of hepatic tumours

    PubMed Central

    Tuttle, Rebecca M; Fox, Justin P; Ouellette, James R; Hellan, Minia

    2014-01-01

    Background The use of radiofrequency ablation (RFA) for cancer is increasing; however, post-discharge outcomes have not been well described. The aim of the present study was to determine rates of hospital-based, acute care utilization within 30 days of discharge after RFA. Methods Using state-level data from California, patients were identified who were at least 40 years of age who underwent RFA of hepatic tumours without a concurrent liver resection from 2007–2011. Our primary outcome was hospital readmissions or emergency department visits within 30 days of discharge. A multivariable regression model was constructed to identify patient factors associated with these events. Results The final sample included 1764 patients treated at 100 centres. Hospital readmissions (11.3/100 discharges), emergency department visits (6.0/100 discharges) and overall acute care utilization (17.3/100 discharges) were common. Most encounters occurred within 10 days of discharge for diagnoses related to the procedure. Patients with renal failure [adjusted odds ratio (AOR) = 1.98 (1.11–3.53)], obesity [AOR = 1.69 (1.03–2.77)], drug abuse [AOR = 2.95 (1.40–6.21)] or those experiencing a complication [AOR = 1.52 (1.07–2.15)] were more likely to have a hospital-based acute care encounter within 30 days of discharge. Conclusions Hospital-based acute care after RFA is common. Patients should be counselled regarding the potential for acute care utilization and interventions targeted to high-risk populations. PMID:24467271

  7. Estrogen-related receptor γ controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol

    PubMed Central

    Jang, Hyun-Hee; Park, Jinyoung; Kim, Jung Ran; Koh, Minseob; Jeong, Won-Il; Koo, Seung-Hoi; Park, Tae-Sik; Yun, Chul-Ho; Park, Seung Bum; Chiang, John Y L; Lee, Chul-Ho; Choi, Hueng-Sik

    2013-01-01

    Background The hepatic endocannabinoid system and cytochrome P450 2E1 (CYP2E1), a key enzyme causing alcohol-induced reactive oxygen species (ROS) generation, are major contributors to the pathogenesis of alcoholic liver disease. The nuclear hormone receptor oestrogen-related receptor γ (ERRγ) is a constitutively active transcriptional activator regulating gene expression. Objective To investigate the role of ERRγ in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERRγ inverse agonist. Design For chronic alcoholic hepatosteatosis study, C57BL/6J wild-type and CB1−/− mice were administered alcohol for 4 weeks. GSK5182 and chlormethiazole (CMZ) were given by oral gavage for the last 2 weeks of alcohol feeding. Gene expression profiles and biochemical assays were performed using the liver or blood of mice. Results Hepatic ERRγ gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERRγ gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERRγ inverse agonist significantly ameliorates chronic alcohol-induced liver injury in mice through inhibition of CYP2E1-mediated generation of ROS, while inhibition of CYP2E1 by CMZ abrogates the beneficial effects of the inverse agonist. Finally, chronic alcohol-mediated ERRγ and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1−/− mice. Conclusions ERRγ, as a previously unrecognised transcriptional regulator of hepatic CB1 receptor, controls alcohol-induced oxidative stress and liver injury through CYP2E1 induction, and its inverse agonist could ameliorate oxidative liver injury due to chronic alcohol exposure. PMID:23023167

  8. The inflammasome in alcoholic hepatitis: its relationship with Mallory-Denk body formation

    PubMed Central

    Peng, Yue; French, Barbara A.; Tillman, Brittany; Morgan, T; French, Samuel W.

    2014-01-01

    Recent studies indicate that the inflammasome activation plays important roles in pathogenesis of alcoholic hepatitis (AH). Nod-like receptor protein 3 (NLRP3) is a key component of the macromolecular complex so called the inflammasome that trigger caspase 1-dependent maturation of the precursors of IL-1β and IL-18 cytokines. It is also known that the adaptor proteins including apoptosis-associated speck-like protein containing CARD (ASC) and the mitochondrial antiviral signaling protein (MAVS) are necessary for NLRP3-dependent inflammasome function. Steatohepatitis frequently includes Mallory-Denk body (MDB) formation. In the case of alcoholic steatohepatitis, MDB formation occurs in 80% of biopsies (French 1981; French 1981). While previous studies have focused on in vitro cell lines and mouse models, we are the first group to investigate inflammasome activation in AH liver biopsy specimen and correlate it with MDB formation. Expression of NOD1, NLRP3, ASC, NAIP, MAVS, Caspase 1, IL-1β, IL-18, and other inflammatory components including IL-6, IL-10, TNF-α, IFN-γ, STAT3, p65 was measured in three to eight formalin-fixed paraffin-embedded AH specimens and control normal liver specimens by immunofluorescence staining and quantified by immunofluorescence intensity. The specimens were double stained with ubiquitin to demonstrate the relationship between inflammasome activation and MDB formation. MAVS, caspase1, IL-18, TNF-α showed increases in expression in AH compared to the controls (p<0.05), and NAIP expression markedly increased in AH compared to the controls (p<0.01). There was a trend that levels of NLRP3, ASC, caspase1, IL-18, IL-10, and p65 expression correlated with the number of MDBs found in the same field of measurement (correlation coefficients were between 0.62 to 0.93, p<0.05). Our results demonstrate the activation of the inflammasome in AH and suggest that MDB could be an indicator of the extent of inflammasome activation. PMID:25149528

  9. [Acute submassive cholestatic hepatitis after treatment with carbimazole. Presentation of a new case and review of the literature].

    PubMed

    Moreno Sánchez, D; Medina Asensio, J; Colina Ruiz-Delgado, F; Campos Cantero, R; Crespo Rincón, L; Belda Serna, A

    1989-09-01

    Carbimazole, an antithyroid agent of the thioimidazole group, can induce unpredictable liver alterations, presumably by hypersensitivity. We describe the case of a hyperthyroid woman who suffered acute submassive cholestatic hepatitis in the course of treatment with this drug. We also review the other seven cases of carbimazole hepatotoxicity previously communicated in the literature. PMID:2682839

  10. Effects of stress, acute alcohol treatment, or both on pre-pulse inhibition in high- and low-alcohol preferring mice

    PubMed Central

    Powers, M.S.; Chester, J.A.

    2014-01-01

    Pre-pulse inhibition of the acoustic startle reflex (PPI) is a measure of sensorimotor gating frequently used to assess information processing in both humans and rodents. Both alcohol and stress exposure can modulate PPI, making it possible to assess how stress and alcohol interact to influence information processing. Humans with an increased genetic risk for alcoholism are more reactive to stressful situations compared to those without a family history, and alcohol may have stress-dampening effects for those with high genetic risk. The purpose of the present study was to examine the effects of stress, acute alcohol exposure, or both on PPI in male and female mice selectively bred for high- (HAP2) and low- (LAP2) alcohol preference. Experiment 1 assessed the effects of various doses of acute alcohol on PPI. Experiments 2 and 3 assessed the effect of 10 days of restraint stress on subsequent PPI tested at 30 min (Experiment 2) or 24 h (Experiment 3) following the termination of stress exposure. Experiment 3 also examined the effects of acute alcohol treatment (0.75 g/kg) on PPI in mice previously exposed to stress or no stress. Results indicate that 0.75 and 1.0 g/kg doses of alcohol increased PPI in HAP2 but not LAP2 mice. When PPI was tested 30 min after stress exposure, stressed HAP2 mice showed a trend toward decreased PPI and stressed LAP2 mice showed a trend toward increased PPI. The combination of stress and alcohol treatment did not alter PPI in either line 24 h following the termination of stress exposure, suggesting that alcohol does not ameliorate the effect of stress on PPI. Stressed LAP2 mice had increased basal circulating corticosterone on the final stress exposure day compared to non-stressed LAP2 mice, and no difference was found between stressed and non-stressed HAP2 mice. The results suggest that high genetic risk for alcoholism may be related to increased sensitivity to alcohol and stress effects on PPI, and this sensitivity could signify an endophenotype for increased genetic risk to develop alcoholism. PMID:24507876

  11. Acute alcohol intoxication and suicide: a gender-stratified analysis of the National Violent Death Reporting System

    PubMed Central

    Kaplan, Mark S; McFarland, Bentson H; Huguet, Nathalie; Conner, Kenneth; Caetano, Raul; Giesbrecht, Norman; Nolte, Kurt B

    2013-01-01

    Objectives Although it is well known that people with alcohol dependence are at a markedly elevated risk for suicide, much less is known about the role of acute alcohol use in suicidal behaviours. The primary aims of this epidemiological study were to assess the prevalence and factors associated with acute alcohol intoxication among 57 813 suicide decedents in 16 states. Methods Data from the restricted National Violent Death Reporting System 2003–2009 for male and female suicide decedents aged 18 years and older were analysed by multiple logistic regression to compare decedents with and without acute alcohol intoxication (defined as blood alcohol concentration (BAC) ≥0.08 g/dl). Results Among men, those who were younger, American Indian/Alaska Native, Hispanic, veterans, of lower educational attainment, deceased from a self-inflicted firearm injury or hanging/suffocation and residing in rural areas were more likely to have been intoxicated at the time of death. Among women, the factors associated with a BAC ≥0.08 g/dl were younger age, being American Indian/Alaska Native, and using a firearm, hanging/suffocation or falling as method of death. Conclusions In both men and women, alcohol intoxication was associated with violent methods of suicide and declined markedly with age, suggesting that addressing risks associated with acute alcohol use may be of the greatest aid in the prevention of violent suicides among young and middle age adults. PMID:22627777

  12. Predicting Acute Viral Hepatitis Serum Markers (A and E) in Patients with Suspected Acute Viral Hepatitis Attending Primary Health Care Centers in Baghdad: A One Year Cross-Sectional Study

    PubMed Central

    Al-Naaimi, Ahmed Samir; Turky, Atallah Mekhlef; Khaleel, Hanan Abdulghafoor; Jalil, Rasha Waleed; Mekhlef, Olah A.; Kareem, Susan Abdul; Hasan, Nadia Yousif; Dhadain, Azhar Abdulla

    2012-01-01

    Background: Viral hepatitis is an important preventable infectious disease with various rates of occurrence in different areas of the world. The main objective of the present study was to evaluate the role of some risk factors in predicting a positive acute viral hepatitis marker among patients with suspected acute viral hepatitis in a primary health care setting in Baghdad. Besides, finding out the occurrence of jaundice, contribution of viruses A and E to the cases that have occurred in Baghdad province was also searched for. Methods: Over a period of 1 year a descriptive cross sectional study was carried out at the primary health care centers in Baghdad. A questionnaire form was used to collect data about demographic factors and the results of the investigations. Total serum bilirubin and bilirubin in urine were done at the primary health care center laboratory. The rest of the sera samples were sent to Hepatitis referral Lab at Central Public Health Laboratory (CPHL) to be tested for anti HAV IgM and anti HEV IgM using ELISA technique. Results: A total of 7,576,372 consultations to primary health care centers were recorded in Baghdad. Among those a total of 2,692 cases (35.5 per 100,000 consultations) were labeled as acute viral hepatitis cases. A positive hepatitis viral marker (A, B, C and E) was found in 1,332 cases (17.6 per 100,000 consultations). More than two fifths (44.8%) of cases were positive for anti-HAV antibodies and another 1.6% had positive anti-HEV antibodies. Conclusion: During 1 year period, the rate of occurrence of suspected acute viral hepatitis cases was 35.5 per 100000 of consultations to the primary health care centers in Baghdad. Of the total suspected cases, only 17.6 per 100000 of the consultations were positive for one of the viral hepatitis markers. Those who tested positive for one of the viral hepatitis markers represent 49.5% of the suspected cases. Proportion of anti HAV IgM positive tests among suspected cases was 44.8%. Factors that were able to predict positive Anti HAV IgM were (younger age group, negative history of cupping or tattooing, negative past history of jaundice). Male gender was the least important predictor of a positive case for anti HAV IgM. Proportion of Anti HEV IgM positive tests among suspected cases was 1.6%. Of the factors studied, only age was able to predict a positive Anti HEV IgM in those more than 15 years. Further studies are recommended. PMID:22980390

  13. Exercise capacity is not impaired after acute alcohol ingestion: a pilot study.

    PubMed

    Popovic, Dejana; Damjanovic, Svetozar S; Plecas-Solarovic, Bosiljka; Pešić, Vesna; Stojiljkovic, Stanimir; Banovic, Marko; Ristic, Arsen; Mantegazza, Valentina; Agostoni, Piergiuseppe

    2014-08-01

    The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated.We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5 g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10 min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00 ± 0.00 to 1.25 ± 0.54‰ (P < 0.001). Basal echocardiographic and spirometric parameters were normal and remained so after acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2 = 3008 ± 638 vs. 2900 ± 543 ml/min, ns; peak workload = 269 ± 53 vs. 249 ± 40 W, ns; test duration 13.7 ± 2.2 vs. 13.3 ± 1.7 min, ns; VE/VCO2 22.1 ± 1.4 vs. 23.3 ± 2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28 ± 2.5 vs. 30.4 ± 3.2, P = 0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17 ± 0.02 vs. 1.14 ± 0.04, P = 0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism. PMID:25083719

  14. Potential Biomarker Peptides Associated with Acute Alcohol-Induced Reduction of Blood Pressure

    PubMed Central

    Wakabayashi, Ichiro; Marumo, Mikio; Nonaka, Daisuke; Shimomura, Tomoko; Eguchi, Ryoji; Lee, Lyang-Ja; Tanaka, Kenji; Hatake, Katsuhiko

    2016-01-01

    The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking. Venous blood was collected from male healthy volunteers before and after drinking white wine (3 ml/kg weight) containing 13% of ethanol. Peptidome analysis for serum samples was performed using a new target plate, BLOTCHIP®. Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. The peptidome analysis showed that the levels of three peptides of m/z 1467, 2380 and 2662 changed significantly after drinking. The m/z 1467 and 2662 peptides were identified to be fragments of fibrinogen alpha chain, and the m/z 2380 peptide was identified to be a fragment of complement C4. The intensities of the m/z 2380 and m/z 1467 peptides before drinking were associated with % decreases in systolic and diastolic blood pressure levels at 45 min after drinking compared with the levels before drinking, while there were no significant correlations between the intensity of the m/z 2662 peptide and % decreases in systolic and diastolic blood pressure levels after drinking. The m/z 1467 and 2380 peptides are suggested to be markers for acute reduction of blood pressure after drinking alcohol. PMID:26815288

  15. Potential Biomarker Peptides Associated with Acute Alcohol-Induced Reduction of Blood Pressure.

    PubMed

    Wakabayashi, Ichiro; Marumo, Mikio; Nonaka, Daisuke; Shimomura, Tomoko; Eguchi, Ryoji; Lee, Lyang-Ja; Tanaka, Kenji; Hatake, Katsuhiko

    2016-01-01

    The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking. Venous blood was collected from male healthy volunteers before and after drinking white wine (3 ml/kg weight) containing 13% of ethanol. Peptidome analysis for serum samples was performed using a new target plate, BLOTCHIP®. Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. The peptidome analysis showed that the levels of three peptides of m/z 1467, 2380 and 2662 changed significantly after drinking. The m/z 1467 and 2662 peptides were identified to be fragments of fibrinogen alpha chain, and the m/z 2380 peptide was identified to be a fragment of complement C4. The intensities of the m/z 2380 and m/z 1467 peptides before drinking were associated with % decreases in systolic and diastolic blood pressure levels at 45 min after drinking compared with the levels before drinking, while there were no significant correlations between the intensity of the m/z 2662 peptide and % decreases in systolic and diastolic blood pressure levels after drinking. The m/z 1467 and 2380 peptides are suggested to be markers for acute reduction of blood pressure after drinking alcohol. PMID:26815288

  16. Patterns of Hepatitis C Virus RNA Levels during Acute Infection: The InC3 Study

    PubMed Central

    Hajarizadeh, Behzad; Grady, Bart; Page, Kimberly; Kim, Arthur Y.; McGovern, Barbara H.; Cox, Andrea L.; Rice, Thomas M.; Sacks-Davis, Rachel; Bruneau, Julie; Morris, Meghan; Amin, Janaki; Schinkel, Janke; Applegate, Tanya; Maher, Lisa; Hellard, Margaret; Lloyd, Andrew R.; Prins, Maria; Dore, Gregory J.; Grebely, Jason

    2015-01-01

    Background 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. Methods 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. Results 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). Conclusions 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 spontaneous clearance. PMID:25837807

  17. Ethylene-vinyl alcohol copolymer endobiliary obliteration of hepatic segments in a patient with isolated bile leaks.

    PubMed

    Wible, Brandt C; Gooden, Christie; Saucier, Nathan; Borsa, John J; Cummings, Lee S; Cho, Kenneth H

    2014-11-01

    A 54-year-old woman with a symptomatic giant hepatic hemangioma underwent an extended left hepatic trisegmentectomy complicated by 250-350 mL/d postoperative bilious drainage. After 5 months of therapy, drainage was unabated, and the patient was no longer a surgical candidate. Sinography revealed three distinct isolated bile duct leaks involving segments 6, 7, and 8. Endobiliary segmentectomy was achieved by obliterating the isolated systems with ethylene-vinyl alcohol copolymer (Onyx; ev3, Plymouth, Minnesota) during three fluoroscopic procedures. Bilious leaks were successfully eliminated, and compensatory hypertrophy of noninvolved liver occurred. At 2 years from the last embolization procedure, the patient remained asymptomatic with no bilious leak. PMID:25442143

  18. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.

    PubMed

    de Jong, W J; Cleveringa, A M; Greijdanus, B; Meyer, P; Heineman, E; Hulscher, J B

    2015-02-01

    The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia. PMID:25559494

  19. Changes in cerebral CB1 receptor availability after acute and chronic alcohol abuse and monitored abstinence.

    PubMed

    Ceccarini, Jenny; Hompes, Titia; Verhaeghen, Anne; Casteels, Cindy; Peuskens, Hendrik; Bormans, Guy; Claes, Stephan; Van Laere, Koen

    2014-02-19

    Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments, but how in vivo CB1R levels are altered in alcoholic patients is still unclear. To assess the short-time effects of a binge drinking episode on CB1R availability, 20 healthy social drinkers underwent [(18)F]MK-9470-positron emission tomography (PET) at baseline and after intravenous ethanol administration (ALC ACU). Moreover, 26 alcoholic patients underwent sequential CB1R PET after chronic heavy drinking (ALC CHR) and after 1 month of abstinence (ALC ABST). Seventeen healthy subjects served as controls. Compared with baseline, ALC ACU resulted in a global increase of CB1R availability (+15.8%). In contrast, a global decreased CB1R availability was found in ALC CHR patients (-16.1%) compared with controls, which remained unaltered after abstinence (-17.0%). Voxel-based analysis showed that ALC CHR patients had reduced CB1R availability, especially in the cerebellum and parieto-occipital cortex. After abstinence, reduced CB1R availability extended also to other areas such as the ventral striatum and mesotemporal lobe. In conclusion, whereas the acute alcohol effect is an increase in CB1R availability, chronic heavy drinking leads to reduced CB1R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature. An enhanced CB1R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction. PMID:24553924

  20. Granular cell tumor of the common hepatic duct presenting as cholangiocarcinoma and acute acalculous cholecystitis.

    PubMed

    Bilanović, D; Boricić, I; Zdravković, D; Randjelović, T; Stanisavljević, N; Toković, B

    2008-01-01

    Granular cell tumors (GCT) are rare benign tumors. Less than 1% of GCTs involve the extrahepatic biliary tree. Most researches favour a Schwann cell origin. Patient, caucasion, female, 31-year-old presented with 4 month history of painless jaundice and pruritus. US and CT revealed dilatation of intrahepatic biliary tree and surgery was performed. Firm tumor mass was found above the conjunction of cystic duct and common hepatic duct (CHD) that caused obstruction and gallblader empyema. The patient underwent radical surgical procedure because Klatskin tumor was clinically suspected. Patohystology and immunohistochemistry confirmed granular cell tumor. Eight years after surgery the patient is wellbeing without symptoms. To our knowledge 69 cases of GCT of the extrahepatic biliary tree have been reported and none of the acute acalculous cholecystitis case acompanied by GCT of CHD. Granular cell tumors are rarely diagnosed preoperatively. Wide resection offers the best chance for cure. PMID:19245149

  1. Immune evasion versus recovery after acute hepatitis C virus infection from a shared source.

    PubMed

    Tester, Ian; Smyk-Pearson, Susan; Wang, Ping; Wertheimer, Anne; Yao, Ermei; Lewinsohn, David M; Tavis, John E; Rosen, Hugo R

    2005-06-01

    Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the determinants of spontaneous resolution versus chronicity remain incompletely understood. In particular, because of the retrospective nature and unknown source of infection in most human studies, direct evidence for emergence of escape mutations in immunodominant major histocompatibility complex class I-restricted epitopes leading to immune evasion is extremely limited. In two patients infected accidentally with an identical HCV strain but who developed divergent outcomes, the total lack of HCV-specific CD4+ T cells in conjunction with vigorous CD8+ T cells that targeted a single epitope in one patient was associated with mutational escape and viral persistence. Statistical evidence for positive Darwinian selective pressure against an immunodominant epitope is presented. Wild-type cytotoxic T lymphocytes persisted even after the cognate antigen was no longer present. PMID:15939788

  2. Alcohol

    MedlinePlus

    ... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  3. Alcohol

    MedlinePlus

    ... Text Size: A A A Listen En Español Alcohol Wondering if alcohol is off limits with diabetes? Most people with diabetes can have a moderate amount of alcohol. Research has shown that there can be some ...

  4. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  5. Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

    PubMed Central

    Delgado, Miguel; Garrido, Francisco; Pérez-Miguelsanz, Juliana; Pacheco, María; Partearroyo, Teresa; Pérez-Sala, Dolores

    2014-01-01

    Abstract Aims: The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease. Results: Using the rat model of d-galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities, and metabolite concentrations suffered more moderate changes following a similar trend. Interestingly, galactosamine treatment induced hepatic nuclear accumulation of methionine adenosyltransferase (MAT) α1 and S-adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact, galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen (APAP) intoxication mimicked most galactosamine effects on hepatic MATα1, including accumulation of nuclear tetramers. H35 cells that overexpress tagged-MATα1 reproduced the subcellular distribution observed in liver, and the changes induced by galactosamine and APAP that were also observed upon glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of tagged-MATα1 induced by these agents correlated with decreased glutathione reduced form/glutathione oxidized form ratios and was prevented by N-acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in epigenetic modifications associated with tagged-MATα1 nuclear accumulation were only prevented by NAC in galactosamine-treated cells. Innovation: Cytoplasmic and nuclear changes in proteins that regulate the methylation index follow opposite trends in acute liver injury, their nuclear accumulation showing potential as disease marker. Conclusion: Altogether these results demonstrate galactosamine- and APAP-induced nuclear accumulation of methionine metabolism enzymes as active oligomers and unveil the implication of redox-dependent mechanisms in the control of MATα1 subcellular distribution. Antioxid. Redox Signal. 20, 2541–2554. PMID:24124652

  6. ACUTE EFFECT OF ETHANOL ON HEPATIC RETICULAR G6Pase AND Ca2+ POOL

    PubMed Central

    Jacobs-Harper, Amy; Crumbly, Ashlee; Romani, Andrea

    2012-01-01

    Background Hydrolysis of glucose 6-phosphate via glucose 6-phosphatase enlarges the reticular Ca2+ pool of the hepatocyte. Exposure of liver cells to ethanol impairs reticular Ca2+ homeostasis. The present study investigated the effect of acute ethanol administration on glucose 6-phosphate supported Ca2+ accumulation in liver cells. Methods Total microsomes were isolated from rat livers acutely perfused with varying doses of ethanol (0.01%, 0.1%, or 1% v/v) for 8 minutes. Calcium uptake was assessed by 45Ca redistribution. Inorganic phosphate (Pi) formation was measured as an indicator of glucose 6-phosphatase hydrolytic activity. Results Glucose 6-phosphate-supported Ca2+ uptake decreased in a manner directly proportional to the dose of ethanol infused in the liver whereas Ca2+ uptake via SERCA pumps was decreased by ~25% only at the highest dose of alcohol administered. The reduced accumulation of Ca2+ within the microsomes resulted in a smaller IP3-induced Ca2+ release. Kinetic assessment of IP3 and passive Ca2+ release indicated a faster mobilization in microsomes from ethanol-treated livers, suggesting alcohol-induced alteration of Ca2+ releasing mechanisms. Pre-treatment of livers with chloromethiazole or dithio-threitol, but not 4-methyl-pyrazole prevented the inhibitory effect of ethanol on glucose 6-phosphatase activity and Ca2+ homeostasis. Conclusions Liver glucose 6-phosphatase activity and IP3-mediated Ca2+ release are rapidly inhibited following acute (8 min) exposure to ethanol, thus compromising the ability of the endoplasmic reticulum to dynamically modulate Ca2+ homeostasis in the hepatocyte. The protective effect of chloromethiazole and di-thio-threitol suggests that the inhibitory effect of ethanol is mediated through its metabolism via reticular cyP4502E1 and consequent free radicals formation. PMID:22958133

  7. Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats

    PubMed Central

    Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei

    2013-01-01

    Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent. PMID:24113767

  8. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

    PubMed Central

    Tuñón, María Jesús; Alvarez, Marcelino; Culebras, Jesús M; González-Gallego, Javier

    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 means of 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. PMID:19575487

  9. Peginterferon alfa related psoriasis in a patient with acute hepatitis C and review of the literature.

    PubMed

    Dag, Muhammed Sait; Oztürk, Zeynel Abidin; Yılmaz, Nimet; Cam, Hakan; Kadayıfçı, Abdurrahman

    2013-09-01

    The Interferon (IFN) which is the standard treatment for Hepatitis C, may cause a lot of side effects including dermatological anomalies. This paper presents a psoriasis case which occurred in relation with the treatment of acute hepatitis C (AHC) with peginterferon alfa (peg-IFN-α). A 60-year-old male patient came to the hospital with symptoms of high liver enzymes. The patient with history of a recent operation showed anti-HCV(+), HCVRNA 3.5 million IU/mL and HCV genotype 1b in the tests. Without any other etiological factors found in the patient, we started a treatment of peg-IFNα-2b with the diagnosis of AHC. After 3 weeks, psoriatic plaques were observed in various parts of the body. Antiviral treatment of the patient was concluded within 6 months. His psoriasis treatment initially commenced with local agents followed by phototherapy. Permanent viral response was seen in the patient and his lesions recovered rapidly after the antipsoriatic and antiviral treatment. Psoriasis and other autoimmune diseases should be considered even though they are encountered rarely,and the patients should be informed of the possible risks before planning treatment with peg-IFN-α. PMID:23912615

  10. Underascertainment of Acute HCV Infections Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System A Case Series and Chart Review

    PubMed Central

    Onofrey, Shauna; Aneja, Jasneet; Haney, Gillian A.; Nagami, Ellen H.; DeMaria, Alfred; Lauer, Georg M.; Hills-Evans, Kelsey; Barton, Kerri; Kulaga, Stephanie; Bowen, Melinda J.; Cocoros, Noelle; McGovern, Barbara H.; Church, Daniel R.; Kim, Arthur Y.

    2016-01-01

    Estimates of the incidence of acute hepatitis C virus (HCV) infection are complicated by the lack of a specific laboratory test and its generally asymptomatic presentation. This study aimed to validate estimates of the incidence of acute HCV infection in Massachusetts. The authors found that acute HCV infection may be underreported when current methods of surveillance are used. Background In 2010, the incidence of hepatitis C virus (HCV) infection in the United States was estimated to be 17 000 cases annually, based on 850 acute HCV cases reported to the Centers for Disease Control and Prevention by local public health authorities. Absence of symptomatic disease and lack of a specific laboratory test for acute infection complicates diagnosis and surveillance. Objective To validate estimates of the incidence of acute HCV infection by determining the reporting rate of clinical diagnoses of acute infection to the Massachusetts Department of Public Health (MDPH) and Centers for Disease Control and Prevention. Design Case series and chart review. Setting Two hospitals and the state correctional health care system in Massachusetts. Patients 183 patients clinically diagnosed with acute HCV infection from 2001 to 2011 and participating in a research study. Measurements Rate of electronic case reporting of acute HCV infection to the MDPH and rate of subsequent confirmation according to national case definitions. Results 149 of 183 (81.4%) clinical cases of acute HCV infection were reported to the MDPH for surveillance classification. The MDPH investigated 43 of these reports as potential acute cases of HCV infection based on their surveillance requirements; ultimately, only 1 met the national case definition and was counted in nationwide statistics published by the Centers for Disease Control and Prevention. Discordance in clinical and surveillance classification was often related to missing clinical or laboratory data at the MDPH as well as restrictive definitions, including requirements for negative hepatitis A and B laboratory results. Limitation Findings may not apply to other jurisdictions because of differences in resources for surveillance. Conclusion Clinical diagnoses of acute HCV infection were grossly underascertained by formal surveillance reporting. Incomplete clinician reporting, problematic case definitions, limitations of diagnostic testing, and imperfect data capture remain major limitations to accurate case ascertainment despite automated electronic laboratory reporting. These findings may have implications for national estimates of the incidence of HCV infection. PMID:26121304

  11. Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.

    PubMed

    van Swelm, Rachel P L; Laarakkers, Coby M M; Blous, Linda; Peters, Janny G P; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; Swinkels, Dorine W; Masereeuw, Rosalinde; Russel, Frans G M

    2012-09-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study was designed to unravel the iron-regulating pathways in mice after APAP-induced hepatotoxicity. Mice with severe injury showed a significant increase in liver iron concentration and oxidative stress. Concurrently, the plasma concentration of hepcidin, the key regulator in iron metabolism, and hepatic hepcidin antimicrobial peptide (Hamp) mRNA expression levels were significantly reduced. We showed that hepcidin transcription was inhibited via several hepcidin-regulating factors, including the bone morphogenetic protein/small mother against decapentaplegic (BMP/SMAD) pathway, CCAAT/enhancer-binding protein α (C/EBPα), and possibly also via erythropoietin (EPO). Downregulation of the BMP/SMAD signaling pathway was most likely caused by hypoxia-inducible factor 1α (HIF-1α), which was increased in mice with severe APAP-induced liver injury. HIF-1α stimulates cleaving of hemojuvelin, the cofactor of the BMP receptor, thereby blocking BMP-induced signaling. In addition, gene expression levels of C/ebpα were significantly reduced, and Epo mRNA expression levels were significantly increased after APAP intoxication. These factors are regulated through HIF-1α during oxidative stress and suggest that HIF-1α is a key modulator in reduced hepcidin transcription after APAP-induced hepatotoxicity. In conclusion, acute APAP-induced liver injury leads to activation of HIF-1α, which results in a downregulation in hepcidin expression through a BMP/SMAD signaling pathway and through C/EBPα inhibition. Eventually, this leads to hepatic iron loading associated with APAP cytotoxicity. PMID:22610607

  12. A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress.

    PubMed

    Elenbaas, Jared S; Maitra, Dhiman; Liu, Yang; Lentz, Stephen I; Nelson, Bradley; Hoenerhoff, Mark J; Shavit, Jordan A; Omary, M Bishr

    2016-05-01

    Protoporphyria is a metabolic disease that causes excess production of protoporphyrin IX (PP-IX), the final biosynthetic precursor to heme. Hepatic PP-IX accumulation may lead to end-stage liver disease. We tested the hypothesis that systemic administration of porphyrin precursors to zebrafish larvae results in protoporphyrin accumulation and a reproducible nongenetic porphyria model. Retro-orbital infusion of PP-IX or the iron chelator deferoxamine mesylate (DFO), with the first committed heme precursor α-aminolevulinic acid (ALA), generates high levels of PP-IX in zebrafish larvae. Exogenously infused or endogenously produced PP-IX accumulates preferentially in the liver of zebrafish larvae and peaks 1 to 3 d after infusion. Similar to patients with protoporphyria, PP-IX is excreted through the biliary system. Porphyrin accumulation in zebrafish liver causes multiorganelle protein aggregation as determined by mass spectrometry and immunoblotting. Endoplasmic reticulum stress and induction of autophagy were noted in zebrafish larvae and corroborated in 2 mouse models of protoporphyria. Furthermore, electron microscopy of zebrafish livers from larvae administered ALA + DFO showed hepatocyte autophagosomes, nuclear membrane ruffling, and porphyrin-containing vacuoles with endoplasmic reticulum distortion. In conclusion, systemic administration of the heme precursors PP-IX or ALA + DFO into zebrafish larvae provides a new model of acute protoporphyria with consequent hepatocyte protein aggregation and proteotoxic multiorganelle alterations and stress.-Elenbaas, J. S., Maitra, D., Liu, Y., Lentz, S. I., Nelson, B., Hoenerhoff, M. J., Shavit, J. A., Omary, M. B. A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress. PMID:26839379

  13. Distinct Features in Natural History and Outcomes of Acute Hepatitis C

    PubMed Central

    Bunchorntavakul, Chalermrat; Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Kaplan, David E.; Nunes, Frederick A.; Aytaman, Ayse; Reddy, K. Rajender

    2015-01-01

    Background: Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. Goals: This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. Study: Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. Results: A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care–associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon α-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. Conclusions: AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance. PMID:24457946

  14. Acute myocardial infarction induced by concurrent use of adderall and alcohol in an adolescent.

    PubMed

    Sharma, Jayendra; de Castro, Carlyle; Chatterjee, Partha; Pinto, Rohit

    2013-01-01

    Adderall (amphetamine, dextroamphetamine mixed salts), a widely prescribed stimulant for the treatment of attention-deficit/hyperactivity disorder in children and adolescents, is considered safe with due precautions. Nonmedical use of Adderall is prevalent and rising in high school and college students. Use of prescribed Adderall without intention to overdose as a cause of myocardial infarction is extremely rare, and to our knowledge, only 3 cases have been reported in the pediatric literature. We report a case of acute myocardial infarction in an adolescent without cardiovascular risk factors who took the total prescribed daily dose of Adderall one time while consuming alcohol. The sporadic use of Adderall with alcohol creates a potentially dangerous situation with serious cardiovascular adverse effects. We should have a high degree of suspicion for children and adolescents on stimulant therapy who present with chest pain and an abnormal electrocardiogram in the pediatric emergency department, and there is a need to evaluate them for myocardial ischemia and infarction. PMID:23283274

  15. Acute myocardial infarction induced by concurrent use of adderall and alcohol in an adolescent.

    TOXLINE Toxicology Bibliographic Information

    Sharma J; de Castro C; Chatterjee P; Pinto R

    2013-01-01

    Adderall (amphetamine, dextroamphetamine mixed salts), a widely prescribed stimulant for the treatment of attention-deficit/hyperactivity disorder in children and adolescents, is considered safe with due precautions. Nonmedical use of Adderall is prevalent and rising in high school and college students. Use of prescribed Adderall without intention to overdose as a cause of myocardial infarction is extremely rare, and to our knowledge, only 3 cases have been reported in the pediatric literature. We report a case of acute myocardial infarction in an adolescent without cardiovascular risk factors who took the total prescribed daily dose of Adderall one time while consuming alcohol. The sporadic use of Adderall with alcohol creates a potentially dangerous situation with serious cardiovascular adverse effects. We should have a high degree of suspicion for children and adolescents on stimulant therapy who present with chest pain and an abnormal electrocardiogram in the pediatric emergency department, and there is a need to evaluate them for myocardial ischemia and infarction.

  16. Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis.

    PubMed

    Gu, H; Werner, J; Bergmann, F; Whitcomb, D C; Büchler, M W; Fortunato, F

    2013-01-01

    The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNFα, IL-6, MCP-1 and IL-10, as early as 3 h after LPS, whereas IL-18 and caspase-1 were evident 24 h later. Alcohol enhanced LPS-induced TNFα expression, whereas blockade of LPS signaling diminished TNFα production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury. PMID:24091659

  17. Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1α overexpression

    PubMed Central

    Morris, E. Matthew; Jackman, Matthew R.; Meers, Grace M. E.; Johnson, Ginger C.; Lopez, Jordan L.; MacLean, Paul S.

    2013-01-01

    Changes in substrate utilization and reduced mitochondrial respiratory capacity following exposure to energy-dense, high-fat diets (HFD) are putatively key components in the development of obesity-related metabolic disease. We examined the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole body energy utilization in obesity-prone (OP) rats. We also examined if hepatic overexpression of peroxisomal proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial respiratory capacity and biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy balance, weight gain, and adiposity, without an increase in liver triglyceride (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole body substrate switching from the dark to the light cycle, which was paired with reductions in hepatic mitochondrial respiration of multiple substrates in multiple respiratory states. Hepatic PGC-1α overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1α overexpression did not alter whole body dietary fatty acid oxidation but resulted in greater storage of dietary free fatty acids in liver lipid, primarily as triacylglycerol. Together, these data demonstrate that a short-term HFD can result in a decrease in metabolic flexibility and hepatic mitochondrial respiratory capacity in OP rats that is completely prevented by hepatic overexpression of PGC-1α. PMID:24091599

  18. Contribution of Hepatitis B to Long-Term Outcome Among Patients With Acute Myocardial Infarction: A Nationwide Study.

    PubMed

    Kuo, Pei-Lun; Lin, Kun-Chang; Tang, Pei-Ling; Cheng, Chin-Chang; Huang, Wei-Chun; Chiang, Cheng-Hung; Lin, Hsiao-Chin; Chuang, Tzu-Jung; Wann, Shue-Ren; Mar, Guang-Yuan; Cheng, Jin-Shiung; Liu, Chun-Peng

    2016-02-01

    Although a possible association between hepatitis B and cardiovascular disease has been identified, the impact of viral hepatitis B on long-term prognosis after an acute myocardial infarction (AMI) is uncertain. Therefore, the aim of our study was to evaluate the specific impact of viral hepatitis B on survival after a first AMI through a retrospective analysis of data from the Taiwan National Health Insurance Research Database.This was a nationwide, propensity score-matched case-control study of patients admitted to hospitals between January 2000 and December 2012 with a primary diagnosis of a first AMI. Among the 7671 prospective patients, 244 patients with a confirmed diagnosis of viral hepatitis B infection were identified. A propensity score, one-to-one matching technique was used to match 244 controls to the AMI group for analysis. Controls were matched on the following variables: sex, age, hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accidents, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention (PCI).Overall, viral hepatitis B infection did not influence the 12-year survival rate (P?=?0.98). However, survival was lower in female patients with viral hepatitis B infection compared to those without (P?=?0.03; hazard ratio, 1.79; 95% confidence interval, 1.08-2.94). Inclusion of percutaneous coronary management improved survival, independent of sex, age, or hepatitis B status.Hepatitis B infection might increase the mortality risk of female patients after a first AMI. PCI may improve the long-term survival of patients after a first AMI, regardless of sex, age, and hepatitis B status. PMID:26844504

  19. Taurine Attenuates Hepatic Inflammation in Chronic Alcohol-Fed Rats Through Inhibition of TLR4/MyD88 Signaling.

    PubMed

    Lin, Chao-Jen; Chiu, Chun-Ching; Chen, Yi-Chen; Chen, Mu-Lin; Hsu, Tsai-Ching; Tzang, Bor-Show

    2015-12-01

    Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and I?B/NF?B compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-?, interleukin (IL)-6, and IL-1? were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling. PMID:26090712

  20. Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation

    PubMed Central

    Forsyth, Christopher B.; Shaikh, Maliha; Cavanaugh, Kate; Tang, Yueming; Vitaterna, Martha Hotz; Song, Shiwen

    2013-01-01

    The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transcriptional and biochemical rhythms in cells and tissues throughout the body. Circadian clock genes have been shown to regulate the physiology and function of the gastrointestinal tract. Disruption of the intestinal epithelial barrier enables the translocation of proinflammatory bacterial products, such as endotoxin, across the intestinal wall and into systemic circulation; a process that has been linked to pathologic inflammatory states associated with metabolic, hepatic, cardiovascular and neurodegenerative diseases many of which are commonly reported in shift workers. Here we report, for the first time, that circadian disorganization, using independent genetic and environmental strategies, increases permeability of the intestinal epithelial barrier (i.e., gut leakiness) in mice. Utilizing chronic alcohol consumption as a well-established model of induced intestinal hyperpermeability, we also found that both genetic and environmental circadian disruption promote alcohol-induced gut leakiness, endotoxemia and steatohepatitis, possibly through a mechanism involving the tight junction protein occludin. Circadian organization thus appears critical for the maintenance of intestinal barrier integrity, especially in the context of injurious agents, such as alcohol. Circadian disruption may therefore represent a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease, as well as other conditions associated with intestinal hyperpermeability and an endotoxin-triggered inflammatory state. PMID:23825629

  1. Early Liver Transplantation for Severe Alcoholic Hepatitis in the United States-A Single-Center Experience.

    PubMed

    Im, G Y; Kim-Schluger, L; Shenoy, A; Schubert, E; Goel, A; Friedman, S L; Florman, S; Schiano, T D

    2016-03-01

    Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p<0.001). Eight recipients are alive at a median of 735 days with 1 alcohol relapse. Early LT for severe AH can achieve excellent clinical outcomes with low impact on the donor pool and low rates of alcohol relapse in highly selected patients in the United States. PMID:26710309

  2. Marked protection against acute renal and hepatic injury after nitrited myoglobin + tin protoporphyrin administration.

    PubMed

    Zager, Richard A

    2015-11-01

    The phenomenon known as renal "ischemic preconditioning," whereby an initial ischemic insult induces resistance against subsequent kidney damage, has been well established in the experimental literature. However, a clinically applicable way to safely recapitulate this state has not been defined. We hypothesized that a unique combination of agents (nitrited myoglobin [N-Mgb] + tin protoporphyrin [SnPP]) can achieve these ends safely and synergistically, increasing cytoprotective proteins (eg, heme oxygenase 1 [HO-1], interleukin 10 [IL-10], and haptoglobin) in kidney cells. To test this hypothesis, CD-1 mice received 1 mg of N-Mgb and 1 ?mol of SnPP, either alone or in combination. Renal cortical HO-1, haptoglobin, and IL-10 gene expressions (messenger RNA [mRNA], protein levels) were determined 4 and 18 hours later. Cytoresistance to 3 forms of acute kidney injury (AKI; glycerol-induced rhabdomyolysis, maleate nephrotoxicity, and postischemic AKI progression to chronic kidney disease [CKD]) was assessed. To ascertain whether cytoresistance might emerge in extrarenal organs, hepatic HO-1, IL-10, and haptoglobin levels were also measured, and resistance to 25 minutes of hepatic ischemia-reperfusion injury and hepatotoxicity (intraperitoneal glycerol injection) was sought. N-Mgb + SnPP induced additive or synergistic increases in renal HO-1, haptoglobin, and IL-10 mRNA and protein levels (up to 20-fold) without inducing any apparent renal or extrarenal damage. After 18 hours of post-treatment, marked or complete protection against glycerol-induced AKI, maleate-induced AKI, and postischemic AKI progression to CKD had emerged. Combined N-Mgb + SnPP was more protective than either agent alone (assessed in glycerol model). N-Mgb + SnPP also upregulated cytoprotective pathways in liver and induced marked protection against both hepatic ischemia-reperfusion and toxic liver damage. In conclusion, we posit that "preconditioning" with combined administration of N-Mgb + SnPP represents a promising approach for protecting against diverse forms of renal and nonrenal (hepatic) forms of tissue damage. PMID:26117289

  3. Acute effects of traditional Japanese alcohol beverages on blood glucose and polysomnography levels in healthy subjects

    PubMed Central

    Kido, Megumi; Asakawa, Akihiro; Koyama, Ken-Ichiro K.; Takaoka, Toshio; Tajima, Aya; Takaoka, Shigeru; Yoshizaki, Yumiko; Okutsu, Kayu; Takamine, Kazunori T.; Sameshima, Yoshihiro

    2016-01-01

    Background. Alcohol consumption is a lifestyle factor associated with type 2 diabetes. This relationship is reportedly different depending on the type of alcohol beverage. The purpose of this study was to examine the acute effects of traditional Japanese alcohol beverages on biochemical parameters, physical and emotional state, and sleep patterns. Methods. Six healthy subjects (three men and three women; age, 28.8 ± 9.5 years; body mass index, 21.4 ± 1.6 kg/m2) consumed three different types of alcohol beverages (beer, shochu, and sake, each with 40 g ethanol) or mineral water with dinner on different days in the hospital. Blood samples were collected before and 1, 2, and 12 h after drinking each beverage, and assessments of physical and emotional state were administered at the same time. In addition, sleep patterns and brain waves were examined using polysomnography. Results. Blood glucose levels at 1 h and the 12-h area under the curve (AUC) value after drinking shochu were significantly lower than that with water and beer. The 12-h blood insulin AUC value after drinking shochu was significantly lower than that with beer. Blood glucose × insulin level at 1 h and the 2-h blood glucose × insulin AUC value with shochu were significantly lower than that with beer. The insulinogenic indexes at 2 h with beer and sake, but not shochu, were significantly higher than that with water. The visual analogue scale scores of physical and emotional state showed that the tipsiness levels with beer, shochu, and sake at 1 h were significantly higher than that with water. These tipsiness levels were maintained at 2 h. The polysomnography showed that the rapid eye movement (REM) sleep latency with shochu and sake were shorter than that with water and beer. Conclusions. Acute consumption of alcohol beverages with a meal resulted in different responses in postprandial glucose and insulin levels as well as REM sleep latency. Alcohol beverage type should be taken into consideration for people with impaired glucose tolerance. PMID:27069795

  4. Acute effects of traditional Japanese alcohol beverages on blood glucose and polysomnography levels in healthy subjects.

    PubMed

    Kido, Megumi; Asakawa, Akihiro; Koyama, Ken-Ichiro K; Takaoka, Toshio; Tajima, Aya; Takaoka, Shigeru; Yoshizaki, Yumiko; Okutsu, Kayu; Takamine, Kazunori T; Sameshima, Yoshihiro; Inui, Akio

    2016-01-01

    Background. Alcohol consumption is a lifestyle factor associated with type 2 diabetes. This relationship is reportedly different depending on the type of alcohol beverage. The purpose of this study was to examine the acute effects of traditional Japanese alcohol beverages on biochemical parameters, physical and emotional state, and sleep patterns. Methods. Six healthy subjects (three men and three women; age, 28.8 ± 9.5 years; body mass index, 21.4 ± 1.6 kg/m(2)) consumed three different types of alcohol beverages (beer, shochu, and sake, each with 40 g ethanol) or mineral water with dinner on different days in the hospital. Blood samples were collected before and 1, 2, and 12 h after drinking each beverage, and assessments of physical and emotional state were administered at the same time. In addition, sleep patterns and brain waves were examined using polysomnography. Results. Blood glucose levels at 1 h and the 12-h area under the curve (AUC) value after drinking shochu were significantly lower than that with water and beer. The 12-h blood insulin AUC value after drinking shochu was significantly lower than that with beer. Blood glucose × insulin level at 1 h and the 2-h blood glucose × insulin AUC value with shochu were significantly lower than that with beer. The insulinogenic indexes at 2 h with beer and sake, but not shochu, were significantly higher than that with water. The visual analogue scale scores of physical and emotional state showed that the tipsiness levels with beer, shochu, and sake at 1 h were significantly higher than that with water. These tipsiness levels were maintained at 2 h. The polysomnography showed that the rapid eye movement (REM) sleep latency with shochu and sake were shorter than that with water and beer. Conclusions. Acute consumption of alcohol beverages with a meal resulted in different responses in postprandial glucose and insulin levels as well as REM sleep latency. Alcohol beverage type should be taken into consideration for people with impaired glucose tolerance. PMID:27069795

  5. Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report.

    PubMed

    Li, Lei; Liu, Yimei; Luo, Tiancheng; Zhou, Jian; Hou, Yingyong; Shen, Xizhong; Wang, Jiyao

    2014-06-01

    The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery. PMID:24810647

  6. Acute Alcohol Use Temporally Increases the Odds of Male Perpetrated Dating Violence: A 90-Day Diary Analysis

    PubMed Central

    Shorey, Ryan C.; Stuart, Gregory L.; McNulty, James K.; Moore, Todd M.

    2013-01-01

    Objective Despite an extensive theoretical literature on acute alcohol intoxication likely increasing the odds of aggression between intimate partners, there have been few temporal studies on the relation between alcohol use and increased odds of intimate partner violence (IPV). Moreover, the literature on the temporal relation between marijuana use and IPV is in its infancy. The existing temporal research has yet to examine in the same study the three distinct types of IPV that occur most often between partners: physical, psychological, and sexual. Thus, the present study examined the temporal relationship between acute alcohol use, marijuana use, and male perpetrated physical, psychological, and sexual dating violence. Method College men who had consumed alcohol in the previous month and were in a current dating relationship participated (N=67). Men completed daily surveys that assessed their alcohol use, marijuana use, and violence perpetration (psychological, physical, and sexual) for up to 90 consecutive days. Results On any alcohol use days, heavy alcohol use days (5 or more standard drinks), and as the number of drinks increased on a given day, the odds of physical and sexual aggression perpetration increased. The odds of psychological aggression increased on heavy alcohol use days only. Marijuana use days did not increase the odds of any type of aggression. Conclusions These findings contribute to a growing body of research on the temporal relation between acute alcohol use and IPV perpetration among college men. Combined with previous research, our findings suggest that dating violence intervention and prevention programs should target reductions in alcohol use. PMID:24199932

  7. Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism.

    PubMed Central

    Vech, R L; Lumeng, L; Li, T K

    1975-01-01

    Individuals with chronic alcohol abuse frequently exhibit lowered plasma levels of pyridoxal 5'-phosphate, the coenzyme form of vitamin B6. Because the liver is the primary source of this coenzyme in plasma and also the principal organ that oxidizes ethanol, the effect of ethanol on hepatic pyridoxal phosphate metabolism was studied in the rat. The chronic feeding of ethanol (36 percent of the total dietary calories) for 6 wk significantly decreased the hepatic pyridoxal phosphate content both in animals given a sufficient amount of vitamin B6 in their diet and in those rendered vitamin B6 deficient. In isolated perfused livers, the addition of 18 mM ethanol lowered the pyridoxal phosphate content of livers from vitamin B6-sufficient animals and deceased the net synthesis of pyridoxal phosphate from pyridoxine by the livers of vitamin B6-deficient animals. Ethanol also diminished the rate of release of pyridoxal phosphate into the perfusate by the livers of vitamin B6-deficient rats. These effects of ethanol, in vitro, were abolished by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase. Thus the derangement of pyridoxal phosphate metabolism produced by ethanol is dependt upon its oxidation. These data support previous findings whic indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate. Images PMID:1168205

  8. Zeaxanthin Dipalmitate Therapeutically Improves Hepatic Functions in an Alcoholic Fatty Liver Disease Model through Modulating MAPK Pathway

    PubMed Central

    Xing, Feiyue; Han, Tao; Jiao, Rui; Liong, Emily C.; Fung, Man-Lung; So, Kwok-Fai; Tipoe, George L.

    2014-01-01

    In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-?B) through the restoration of its inhibitor kappa B alpha (I?B?), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases. PMID:24740309

  9. Acute alcohol administration improves skilled reaching success in intact but not 6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and anxiolytic effects of alcohol.

    PubMed

    Metz, Gerlinde A; Gonzalez, Claudia L R; Piecharka, Dionne M; Whishaw, Ian Q

    2003-06-16

    Low doses of alcohol impair movement and reduce anxiety. Most assessments of movement under ethyl alcohol (alcohol) in the rat have been tests of whole body movements, however. There has been no examination of the effects of alcohol on skilled limb movements, such as reaching for food with a forelimb. This was the purpose of the present study. Rats were trained to reach through a slot of a box with a forelimb in order to obtain a food pellet located on an external shelf. Once asymptotic performance was achieved, rats were given alcohol (20 ml of 8, 12 or 20% (v/v) solution) in separate tests to establish a relationship between alcohol ingestion and skilled reaching performance. Acute treatment with all doses of alcohol impaired postural support, but doses of 8 and 12% alcohol improved skilled reaching success. Qualitative analysis of the movements used for reaching at doses of 8 and 12% indicated that some limb components of the reaching movement were also impaired, perhaps secondarily due to impaired posture. In contrast, the reaching success of rats with unilateral dopamine depletion, induced with the neurotoxin 6-hydroxydopamine (6-OHDA) in the nigrostriatal bundle, was impaired by the same dose of alcohol that improved reaching success in control rats. The finding of improved success in reaching associated with reduced postural support in normal rats suggests a differential action of alcohol on movement subsystems underlying posture relative to skilled movement that depends upon an intact dopaminergic system. The results are also discussed with respect to the relationship of subsystems of movement and anxiety. PMID:12798278

  10. Hepatoprotective and anti-hepatitis C viral activity of Platycodon grandiflorum extract on carbon tetrachloride-induced acute hepatic injury in mice.

    PubMed

    Kim, Tae-Won; Lim, Jong-Hwan; Song, In-Bae; Park, Sang-Jin; Yang, Jae-Won; Shin, Jung Cheul; Suh, Joo-Won; Son, Hwa-Young; Cho, Eun-Sang; Kim, Myoung-Seok; Lee, Sang-Wook; Kim, Jong-Woo; Yun, Hyo-In

    2012-01-01

    The present study aims to evaluate the anti-HCV activity of hotwater extract from Platycodon grandiflorum (BC703) with HCV genotype 1b subgenomic replicon system and investigate its hepatoprotective activity on carbon tetrachloride (CCl(4))-induced acute liver damage in mice. BC703 produced significant hepatoprotective effects against CCl(4)-induced acute hepatic injury by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation. Histopathological studies further substantiated the protective effect of BC703. Furthermore, BC703 inhibited the HCV RNA replication with an EC(50) value and selective index (CC(50)/EC(50)) of 2.82 µg/mL and above 35.46, respectively. However, digested BC703 using a simulated gastric juice showed poor protective effect against CCl(4)-induced hepatotoxicity in mice and decreased anti-HCV activity as compared to the intact BC703. Although further studies are necessary, BC703 may be a beneficial agent for the management of acute hepatic injury and chronic HCV infection. PMID:22878389

  11. Serological misdiagnosis of acute liver failure associated with echovirus 25 due to immunological similarities to hepatitis A virus and prozone effect.

    PubMed

    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. PMID:25355762

  12. Application of an Alcohol Clamp Paradigm to Examine Inhibitory Control, Subjective Responses and Acute Tolerance in Late Adolescence

    PubMed Central

    Hendershot, Christian S.; Wardell, Jeffrey D.; Strang, Nicole M.; Markovich, Mike S.D.; Claus, Eric D.; Ramchandani, Vijay A.

    2015-01-01

    Individual differences in acute alcohol effects on cognitive control and subjective responses—and acute tolerance to these effects—are implicated in the risk for heavy drinking and alcohol-related harms. Few studies have examined these effects in drinkers under age 21. Additionally, studies of acute tolerance typically involve bolus oral alcohol administration, such that estimates of tolerance are confounded with blood alcohol concentration (BAC) limb. The current study examined cognitive control and subjective responses in young heavy drinkers (n = 88, M = 19.8 years old [SD = 0.8]) during a single-session alcohol clamp protocol. Participants completed an intravenous alcohol session comprising an ascending limb (0 to 80mg% in 20 minutes) and a BAC plateau (80mg% for 80 minutes). Serial assessments included a cued go/no-go task and measures of stimulation, sedation and craving. Relevant individual difference factors (ADHD symptoms and sensation seeking) were examined as moderators. Multi-level modeling demonstrated that response inhibition worsened following initial rise in BAC and showed increasing impairment during the BAC plateau. ADHD symptoms and sensation seeking moderated this effect. Significant within-person associations between stimulation and craving were evident on the ascending limb only. Participants with higher ADHD symptoms reported steeper increases in stimulation during the ascending limb. These findings provide initial information about subjective and behavioral responses during pseudo-constant BAC, and potential moderators of these outcomes, in late adolescence. Additional studies with placebo-controlled designs are necessary to confirm these findings. PMID:26053322

  13. A rare case of acute hepatitis induced by use of Babchi seeds as an Ayurvedic remedy for vitiligo.

    PubMed

    Smith, Deborah Ann; MacDonald, Stewart

    2014-01-01

    This case highlights that hepatitis is a potential side effect of Babchi seeds, an Ayurvedic remedy used to treat vitiligo. The patient, a 52-year-old Indian woman, presented with a 1 week history of jaundice, vomiting, pruritus and abdominal pain. Progressive deterioration in liver function prompted a liver biopsy which was consistent with the diagnosis of a drug-induced hepatitis. The hepatitis resolved after withdrawal of its use. A PubMed search found no previous UK cases and only two cases have been reported globally. This potentially serious side effect of a widely available substance is not acknowledged by manufacturers, and those purchasing the product are unaware of the risk of harm. To compound this risk, there is an absence of dosing advice or maximum recommended daily intake. It is important to ask about topical and oral herbal remedies in cases of acute jaundice as patients rarely perceive these preparations as 'medications'. PMID:25103314

  14. Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection

    PubMed Central

    Cho, Yoo-Kyung; Kim, Young Nam

    2014-01-01

    Background/Aims This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ≥12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance. Methods Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy. Results HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ≥2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy. Conclusions Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ≥2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis. PMID:25548743

  15. The effect of acute alcohol on motor-related EEG asymmetries during preparation of approach or avoid alcohol responses.

    PubMed

    Korucuoglu, Ozlem; Gladwin, Thomas E; Wiers, Reinout W

    2016-02-01

    Alcohol-approach tendencies have been associated with heavy drinking and play a role in the transition to alcohol abuse. Such cognitive biases might predict future alcohol use better under a low dose of alcohol. The aim of this prospective study was to investigate both the magnitude and the predictive power of alcohol-induced changes on approach-avoidance bias and bias-related cortical asymmetries during response preparation across heavy and light drinking adolescents. In heavy drinking adolescents greater approach-related asymmetry index in the beta-band was observed for soft-drink cues compared to alcohol ones and this increase was associated with increase in difficulty to regulate alcohol intake. Earlier findings demonstrated that young heavy drinkers hold both positive and negative implicit alcohol associations, reflecting an ambiguity towards alcohol. The increase in approach related beta-lateralization for soft-drink cues measured in this study may represent a compensatory effort for the weaker S-R mapping (approaching soft drink). The MRAA findings in this study may highlight a mechanism related to overcompensation due to ambivalent attitudes towards drinking in our heavy drinking sample who had greater problems to limit their alcohol intake compared to light drinkers. Moreover, a relatively strong approach soft-drink and weak approach alcohol reaction-time bias after alcohol predicted decreasing drinking; suggesting that the capacity to control the bias under alcohol could be a protective factor. PMID:26762699

  16. Acute alcohol effects on attentional bias are mediated by subcortical areas associated with arousal and salience attribution.

    PubMed

    Nikolaou, Kyriaki; Field, Matt; Critchley, Hugo; Duka, Theodora

    2013-06-01

    Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the underlying cognitive and brain mechanisms remain unknown. We combined functional magnetic resonance imaging (fMRI) with performance of a dual task that probed attentional distraction by alcohol-related stimuli during 'conflict' processing: the Concurrent Flanker/Alcohol-Attentional bias task (CFAAT). In this task, an Eriksen Flanker task is superimposed on task-unrelated background pictures with alcohol-associated or neutral content. Participants respond to the direction of a central 'target' arrow and ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) 'flanking' arrows. Using a between-subject design, 40 healthy moderate-to-heavy social drinkers received either no alcohol (placebo), 0.4?g/kg (low dose), or 0.8?g/kg (high dose) of alcohol, and underwent fMRI while performing the CFAAT. The low alcohol dose, relative to placebo, increased response latencies on trials with alcohol-associated backgrounds and, under low cognitive load, increased the activity evoked by these pictures within a medial hypothalamic region. Under high cognitive load, the low alcohol dose, relative to placebo, elicited greater activity within a more lateral hypothalamic region, and reduced activity within frontal motor areas. The high alcohol dose, relative to placebo, did not reliably affect response latencies or neural responses to background images, but reduced overall accuracy under high cognitive load. This effect correlated with changes in reactivity within medial and dorsal prefrontal cortices. These data suggest that alcohol at a low dose primes attentional bias to alcohol-associated stimuli, an effect mediated by activation of subcortical hypothalamic areas implicated in arousal and salience attribution. PMID:23361162

  17. Serological cross reactivity to CMV and EBV causes problems in the diagnosis of acute hepatitis E virus infection.

    PubMed

    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. PMID:24402843

  18. Ecological Momentary Assessment of Acute Alcohol Use Disorder Symptoms: Associations With Mood, Motives, and Use on Planned Drinking Days

    PubMed Central

    Dvorak, Robert D.; Pearson, Matthew R.; Day, Anne M.

    2015-01-01

    Several theories posit that alcohol is consumed both in relation to one’s mood and in relation to different motives for drinking. However, there are mixed findings regarding the role of mood and motives in predicting drinking. Ecological momentary assessment (EMA) methods provide an opportunity to evaluate near real-time changes in mood and motives within individuals to predict alcohol use. In addition, endorsement of criteria of an alcohol use disorder (AUD) may also be sensitive to changes within subjects. The current study used EMA with 74 moderate drinkers who responded to fixed and random mood, motive, alcohol use, and AUD criteria prompts over a 21-day assessment period. A temporal pattern of daytime mood, evening drinking motivation, and nighttime alcohol use and acute AUD symptoms on planned drinking days was modeled to examine how these associations unfold throughout the day. The results suggest considerable heterogeneity in drinking motivation across drinking days. Additionally, an affect regulation model of drinking to cope with negative mood was observed. Specifically, on planned drinking days, the temporal association between daytime negative mood and the experience of acute AUD symptoms was mediated via coping motives and alcohol use. The current study found that motives are dynamic, and that changes in motives may predict differential drinking patterns across days. Further, the study provides evidence that emotion-regulation-driven alcohol involvement may need to be examined at the event level to fully capture the ebb and flow of negative affect motivated drinking. PMID:24932896

  19. Liver diseases by alcohol and hepatitis C: early detection and new insights in pathogenesis lead to improved treatment.

    PubMed

    Lieber, C S

    2001-01-01

    Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of treatment. Therapy must include correction of nutritional deficiencies, while taking into account changes of nutritional requirements. Methionine is normally activated to S-adenosylmethionine (SAMe). However, in liver disease, the corresponding enzyme is depressed. The resulting deficiencies can be attenuated by the administration of SAMe but not by methionine. Similarly, phosphatidylethanolamine methyltransferase activity is depressed, but the lacking phosphatidylcholine (PC) can be administrated as polyenylphosphatidylcholine (PPC). Chronic ethanol consumption increases CYP2E1, resulting in increased generation of toxic acetaldehyde and free radicals, tolerance to ethanol and other drugs, and multiple ethanol-drug interactions. Experimentally, PPC opposes CYP2E1 induction and fibrosis. Alcoholism and hepatitis C infection commonly co-exist, with acceleration of fibrosis, cirrhosis, and hepatocellular carcinoma. PPC is being tested clinically as a corresponding antifibrotic agent. Available antiviral agents are contraindicated in the alcoholic. Anti-inflammatory agents, such as steroids, may be selectively useful. Finally, anticraving agents, such as naltrexone or acamprosate, should be part of therapy. PMID:11268819

  20. CHRONIC ALCOHOL CONSUMPTION HAS BIPHASIC EFFECTS ON HEPATIC INSULIN SIGNALING DEPENDENT ON DOSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies have shown paradoxical biphasic effects of alcohol on health. Moderate drinkers have lower overall mortality than teetotalers or than heavy drinkers. There are protective effects of low levels of alcohol consumption (less than one drink day) on diabetes risk and other chroni...

  1. Hepatitis

    MedlinePlus

    ... fever, fatigue, lack of appetite, nausea, jaundice and dark urine.These symptoms can last up to five ... fever, fatigue, lack of appetite, nausea, jaundice and dark urine. Acute symptoms can last several months, during ...

  2. Alcoholism.

    ERIC Educational Resources Information Center

    Caliguri, Joseph P., Ed.

    This extensive annotated bibliography provides a compilation of documents retreived from a computerized search of the ERIC, Social Science Citation Index, and Med-Line databases on the topic of alcoholism. The materials address the following areas of concern: (1) attitudes toward alcohol users and abusers; (2) characteristics of alcoholics and

  3. Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark

    PubMed Central

    Rex, Karsten Fleischer; Krarup, Henrik Bygum; Laurberg, Peter; Andersen, Stig

    2016-01-01

    Background Hepatitis B virus (HBV) infection is common in Arctic populations and high alcohol intake has been associated with an increased risk of a number of diseases. Yet, a description of the influence of alcohol intake in persons with HBV infection on liver biochemistry is lacking. Objective We aimed to describe the association between reported alcohol intake and liver biochemistry taking into account also HBV infection, ethnicity, Inuit diet, body mass index (BMI), gender and age in an Arctic population. Design and methods Population-based investigation of Inuit (n=441) and non-Inuit (94) in Greenland and Inuit living in Denmark (n=136). Participants filled in a questionnaire on alcohol intake and other life style factors. Blood samples were tested for aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, hepatitis B surface antigen, hepatitis B surface antibody and hepatitis B core antibody. We also performed physical examinations. Results Participation rate was 95% in Greenland and 52% in Denmark. An alcohol intake above the recommended level was reported by 12.9% of non-Inuit in Greenland, 9.1% of Inuit in East Greenland, 6.1% of Inuit migrants and 3.4% of Inuit in the capital of Greenland (p=0.035). Alcohol intake was associated with AST (p<0.001) and GGT (p=0.001), and HBV infection was associated with ALP (p=0.001) but not with AST, GGT, bilirubin or albumin in the adjusted analysis. Inuit had higher AST (p<0.001), GGT (p<0.001) and ALP (p=0.001) values than non-Inuit after adjustment for alcohol, diet, BMI and HBV exposure. Ethnic origin modified the association between alcohol and AST, while HBV infection did not modify the associations between alcohol and liver biochemistry. Conclusions Non-Inuit in Greenland reported a higher alcohol intake than Inuit. Ethnic origin was more markedly associated with liver biochemistry than was alcohol intake, and Greenlandic ethnicity modified the effect of alcohol intake on AST. HBV infection was slightly associated with ALP but not with other liver biochemistry parameters. PMID:26928535

  4. Liver Transplantation for Acute Intermittent Porphyria is Complicated by a High Rate of Hepatic Artery Thrombosis

    PubMed Central

    Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

    2012-01-01

    Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195–200, 2012. © 2011 AASLD. PMID:21618697

  5. Protection of Gastrointestinal Mucosa from Acute Heavy Alcohol Consumption: The Effect of Berberine and Its Correlation with TLR2, 4/IL1β-TNFα Signaling

    PubMed Central

    Du, Feng; Chai, Yu-Shuang; Jiang, Jing-Fei; Wang, Yu-Gang; Yu, Xuan; Yan, Xiao-Jin; Xing, Dong-Ming; Du, Li-Jun

    2015-01-01

    The purpose of the present study is to confirm the protective effect of berberine (BBR) on gastrointestinal injury caused by acute heavy alcohol exposure, an effect that has not been reported previously. Our research details how BBR protects against gastrointestinal injuries from acute alcohol exposure using both in vivo and in vitro experiments. Acute high alcohol concentrations lead to obvious damage to the gastrointestinal mucosa, resulting in necrosis of the intestinal mucosa. Oral administration of BBR was able to significantly reduce this alcohol-induced damage, inhibit increases of alcohol-induced TNFα and IL-1β expression in gastrointestinal mucosa as well as their upstream signals TLR2 and TLR4, and regulate cytokines that modulate tight junctions. Alcohol consumption is a popular human social behavior worldwide, and the present study reports a comprehensive mechanism by which BBR protects against gastrointestinal injuries from alcohol stress, providing people with a novel application of BBR. PMID:26226164

  6. Interactive effects of contextual cues and acute alcohol intoxication on the associations between alcohol expectancy activation and urge to drink.

    PubMed

    Wardell, Jeffrey D; Read, Jennifer P

    2014-10-01

    This study examined the joint effects of contextual cues and alcohol intoxication on the associations between activation of positive and negative alcohol expectancies in memory and self-reported urges to drink alcohol after a laboratory alcohol administration. Young adult heavy drinkers were randomly assigned to drink a moderate dose of alcohol or a placebo (alcohol manipulation), and then listened to positive or negative drinking scenarios (cue manipulation). Before and after these manipulations, participants completed an alcohol expectancy Stroop task assessing positive and negative expectancy activation, as well as self-report measures of urges to drink. Regression analyses revealed that the alcohol and cue manipulations had a joint, moderating impact on the associations between expectancy activation and postcue changes in urge to drink. Specifically, both increased activation of negative expectancies and decreased activation of positive expectancies predicted decreases in urges to drink, but only for intoxicated participants in the negative cue condition. There were no associations between expectancy activation and urges to drink for those in the positive cue condition regardless of beverage condition. Results suggest that whether memory activation of alcohol expectancies has an impact on urge to drink after alcohol is on board may depend on the relevance of the activated expectancies to the current drinking context. This process appears to be influenced by a complex interaction between contextual cues in the environment and the pharmacological effects of alcohol. PMID:25111186

  7. Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing cytochrome p450 2E1 induction in rodent models.

    PubMed

    Stice, Camilla P; Liu, Chun; Aizawa, Koichi; Greenberg, Andrew S; Ausman, Lynne M; Wang, Xiang-Dong

    2015-04-15

    Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD. PMID:25592162

  8. Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model

    PubMed Central

    GLAZER, EVAN S; ZHU, CIHUI; HAMIR, AMIR N.; BORNE, AGATHA; THOMPSON, C. SHEA; CURLEY, STEVEN A.

    2012-01-01

    There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 hours after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy. PMID:20854190

  9. Acute hepatitis C virus infection in a nurse trainee following a needlestick injury.

    PubMed

    Scaggiante, Renzo; Chemello, Liliana; Rinaldi, Roberto; Bartolucci, Giovanni Battista; Trevisan, Andrea

    2013-01-28

    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

  10. [Coping strategies used by the family of a patient with acute fulminant hepatitis].

    PubMed

    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. PMID:22746001

  11. Acute type A, B, and non-A, non-B hepatitis in a hospital population in London: clinical and epidemiological features.

    PubMed Central

    Bamber, M; Thomas, H C; Bannister, B; Sherlock, S

    1983-01-01

    The aetiology of acute viral hepatitis in 172 patients admitted to an infectious diseases hospital in North London was: hepatitis A in 88 (51%), hepatitis B in 58 (34%), Epstein-Barr (EB) virus in four (2%) and non-A, non-B in 22 (13%). NANB hepatitis was a milder disease than that associated with the other viruses. It predominantly occurred in young men (77%). In half of the cases there was evidence of parenteral transmission. It was not transmitted by sexual contact. PMID:6303917

  12. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    SciTech Connect

    Chen Bo; Xia Jing; Li Guangxing; Zhou Yifeng

    2010-03-15

    Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unit responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.

  13. Induction of hepatic Bach1 mRNA expression by carbon tetrachloride-induced acute liver injury in rats

    PubMed Central

    TANIOKA, NOHITO; SHIMIZU, HIROKO; TAKAHASHI, TORU; OMORI, EMIKO; KURODA, KOSUKE; SHIBATA, MARI; YAMAOKA, MASAKAZU; TODA, YUICHIRO; MATSUSAKI, TAKASHI; MORIMATSU, HIROSHI

    2014-01-01

    Hepatic oxidative stress is a major contributor to the pathogenesis of several acute liver diseases. Diagnostic markers of hepatic oxidative stress may facilitate early detection and intervention. Bach1 is an oxidative stress-responsive transcription factor that represses heme oxygenase 1 (HO-1), the rate-limiting enzyme in the catabolism of heme, a potent pro-oxidant. We previously demonstrated that carbon tetrachloride (CCl4) causes oxidative hepatic injury in rats, exacerbated by free heme, suggesting that CCl4 may affect Bach1 gene expression. In the present study, we used northern blot analysis to measure Bach1, HO-1 and δ-aminolevulinate synthase (ALAS1; a heme biosynthesis enzyme) mRNA expression levels during acute hepatic injury induced by CCl4 (at doses of 0.1, 1.0 and 2.0 ml/kg body weight). Oxidative injury was assessed by measuring serum alanine aminotransferase (ALT), hepatic malondialdehyde (MDA) and glutathione (GSH) content. Treatment with CCl4 induced a significant dose-dependent increase in Bach1 mRNA 1–3 h after administration. Bach1 mRNA peaked at 6 h after CCl4 treatment (1 ml/kg), followed by a rapid decrease and gradual return to baseline by 12 h after treatment. The timecourse of transient Bach1 mRNA induction roughly mirrored that of HO-1 mRNA, while ALAS1 mRNA was inversely downregulated. Serum ALT levels and hepatic MDA concentration were significantly increased at 24 h after CCl4 treatment, while the hepatic GSH content was significantly reduced within 3 h of treatment. Serum ALT levels were positively correlated with Bach1 mRNA levels. These findings indicate that Bach1 mRNA is transiently induced in rat liver by CCl4, possibly as a regulatory mechanism to restore HO-1 to baseline following free heme catabolism. Our findings also suggest that Bach1 mRNA expression may be a novel indicator of the extent of oxidative hepatic injury caused by free heme. PMID:24748974

  14. Kinetics and mechanisms of hepatic acute phase response to subtotal partial hepatectomy and cultural impact on environmental hepatic end-stage liver injury in the homeless.

    PubMed

    Fouad, F M; Mamer, O A; Sauriol, F; Ruhenstroth-Bauer, G

    2001-06-01

    Intoxication and liver damage induced by carbon tetrachloride (CCl(4)), aflatoxin B1, diabetes, and subtotal partial hepatectomy (PH(90)) in rats in which approximately 90% of the total hepatic tissue mass is surgically removed produces an acute-phase response (APR) whose initial stage prior to regression closely mimics the APRs associated with the life-threatening hepatic failure seen in the homeless. Rats treated by PH(90)were either healthy, CCl(4)-intoxicated, diabetic, or alflatoxin B1 (AFB1) intoxicated to the point of 75% liver insufficiency. It is well documented that high rates of mortality following PH(90)in aseptic rats could be minimized by supplementing drinking water with 20% glucose, organic components of L-15 medium and housing animals in cages maintained at 33-35;C. Aseptic rats showed a mild 20-30% decrease in APR proteins during the first 4-5 days following PH(90), while a maximal APR was noted 9-12 days post PH(90)and lasted for ~30 days when it returned to values close to those of healthy controls. This delay in hepatic APR of the remnant caudate lobe favoured replacement of lost basophilic clumps and ribosomes. The newly synthesized ribosomes of the nascent hepatocytes quantitatively maintained the APR signals of the injured caudate hepatocytes, and biosynthesized and released a typical spectrum of APR proteins. We suggest that massively injured liver has decoded an already stored and irreversible DNA-biochemical sequence of events in which priority is given to recovery of lost tissues by delaying an APR response to injury. In PH(90)of diabetic and CCl(4)-intoxicated rats, the hepatic dual functions of regeneration and APR processes associated with intoxication-initiated catabolic signals, created a heavy metabolic burden on the remnant caudate lobe leading to higher rates of mortality. APR of healthy rats to AFB1 parallels that of alpha-amanitin-induced intoxication. Similarly, within shorter time scale proportional to the severity of surgery, livers undergoing 75% partially hepatectomy (PH(75)) delayed both the onset and regression of APR. We are therefore led to believe that approaches other than liver transplantation should be considered as viable alternatives in the treatment of various acute and chronic liver diseases to avoid rejection and retransplantation. Scarcity of cadaveric liver has forced the medical community to investigate xenotransplantation with its unknown risks. Concomitantly, it is suggested that in view of the incalculable risks of indifference, the homeless must receive much improved medical care as we have found that two-dimensional immunoelectrophoretic assay of their serum is indicative of acute and chronic liver injury. The scientific and moral interrelationships of related matters are illuminated. PMID:11399123

  15. Phosphorus-31 nuclear magnetic resonance spectroscopic study of the canine pancreas: applications to acute alcoholic pancreatitis

    SciTech Connect

    Janes, N.; Clemens, J.A.; Glickson, J.D.; Cameron, J.L.

    1988-01-01

    The first nuclear magnetic resonance spectroscopic study of the canine pancreas is described. Both in-vivo, ex-vivo protocols and NMR observables are discussed. The stability of the ex-vivo preparation based on the NMR observables is established for at least four hours. The spectra obtained from the in-vivo and ex-vivo preparations exhibited similar metabolite ratios, further validating the model. Metabolite levels were unchanged by a 50% increase in perfusion rate. Only trace amounts of phosphocreatine were observed either in the intact gland or in extracts. Acute alcoholic pancreatitis was mimicked by free fatty acid infusion. Injury resulted in hyperamylasemia, edema (weight gain), increased hematocrit and perfusion pressure, and depressed levels of high energy phosphates.

  16. Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense.

    PubMed

    Jiang, Zhihui; Chen, Chen; Wang, Jian; Xie, Wenyan; Wang, Meng; Li, Xinsheng; Zhang, Xiaoying

    2016-01-01

    Alcoholic liver disease (ALD) is a serious and challenging health issue. In the past decade, natural components possessing hepatoprotective properties have gained more attention for ALD intervention. In this study, the phytochemical components of anthocyanins from purple potato were assessed using UPLC-MS/MS, and the hepatoprotective effects of purple potato anthocyanins (PPAs) were investigated in the ALD mouse model. Serum and liver biochemical parameters were determined, along with histopathological changes in liver tissue. In addition, the major contributors to alcohol-induced oxidative stress were assessed. The results indicated that the levels of aspartate transaminase and alanine transaminase were lower in the serum of the PPA-treated group than the alcohol-treated group. PPAs significantly inhibited the reduction of total cholesterol and triglycerides. Higher levels of superoxide dismutase and reduced glutathione enzymes as well as a reduction in the formation of malondialdehyde occurred in mice fed with PPAs. In addition, PPAs protected against increased alcohol-induced levels and activity of cytochrome P450 2E1 (CYP2E1), which demonstrates the effects of PPAs against alcohol-induced oxidative stress and liver injury. This study suggests that PPAs could be an effective therapeutic agent in alcohol-induced liver injuries by inhibiting CYP2E1 expression and thereby strengthening antioxidant defenses. PMID:26481011

  17. Biochemical Evaluation of Patients of Alcoholic Liver Disease and Non-alcoholic Liver Disease.

    PubMed

    Torkadi, Prasad P; Apte, I C; Bhute, A K

    2014-01-01

    Alcoholic liver disease (ALD) is due to excessive alcohol intake for long duration. Distinguishing ALD from non-ALD (non-alcoholic steatohepatitis, hepatitis of viral origin) is difficult as patient may deny alcohol abuse. Clinical examination, histology and serology may not differentiate these conditions. Accurate diagnosis is important as management of ALD differs from non-ALD patients. The aim of our study was (1) To evaluate the patients of ALD and non-ALD by biochemical parameters compared to controls, (2) To assess whether these parameters can differentiate ALD from non-ALD. Study was carried out on 50 patients of ALD in group I and 35 patients of NASH (non-alcoholic steatohepatitis) and acute viral hepatitis each in group II. Age matched healthy controls n=50. Selection criteria-history of alcohol intake (amount and duration), clinical examination, sonography of abdomen, serum alanine transaminase (ALT) and bilirubin levels. Blood samples were analyzed for bilirubin, aspartate transaminase (AST), ALT, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) by kinetic method. Statistical analysis was done by Student unpaired 't' test. Patients of ALD have raised AST/ALT ratio (De Ritis ratio) (>2), ALP and GGT compared to controls (P<0.01).There is significant difference in AST/ALT ratio, serum GGT and ALP in ALD group compared to that in NASH and acute viral hepatitis (P<0.05). This study suggests that De Ritis ratio>2 in ALD patients may be due to alcohol induced hepatic mitochondrial injury and pyridoxine deficiency. High GGT and ALP values may indicate enzyme induction by alcohol and mild cholestasis. Thus ALD patients have severe hepatic damage. De Ritis ratio<1 and normal to mild elevation in GGT level in NASH and acute viral hepatitis suggest mild hepatic injury of non-alcoholic origin. Our study concludes that ALD patients can be differentiated from NASH and acute viral hepatitis with certainty by measuring serum AST/ALT ratio, GGT and ALP. These biochemical parameters may help clinicians to support the diagnosis of ALD and non-ALD. PMID:24478554

  18. Acute Alcohol Intoxication in Patients with Mild Traumatic Brain Injury: Characteristics, Recovery, and Outcome.

    PubMed

    Scheenen, Myrthe E; de Koning, Myrthe E; van der Horn, Harm J; Roks, Gerwin; Yilmaz, Tansel; van der Naalt, Joukje; Spikman, Jacoba M

    2016-02-15

    A substantial number of patients (30% to 50%) sustains a mild traumatic brain injury (mTBI) while they are under the influence of alcohol. An acute alcohol intoxication (AAI) at the time of injury has been subject of research in severe TBI, but little is known about the relation between AAI and mTBI. This study aimed to describe the characteristics of this intoxicated subgroup and evaluate recovery and outcome in comparison to sober mTBI patients. We included 528 mTBI patients (Glasgow Coma Scale [GCS] score 13-15) admitted to two Level 1 trauma centers as part of a prospective follow-up study. We compared clinical characteristics, demographics, and injury mechanism between groups. Post-concussive complaints, mood disorders, and post-traumatic stress-related complaints were assessed at 2 weeks post-injury, and outcome at 6 months with the Glasgow Outcome Scale Extended (GOSE). Thirty-three percent of the mTBI patients were intoxicated. Results showed that the intoxicated group was younger (36 vs. 40 years; p = 0.001) and were more frequently of male gender (78% vs. 60%; p < .001). The groups also differed in injury related characteristics, with intoxicated patients more frequently sustaining falls or violence-related injuries. The intoxicated group was assessed with a lower GCS score and had a higher hospital admission rate. However, at 2 weeks post-injury, intoxicated patients reported less complaints than the non-alcohol group and showed a better recovery at 6 months (average GOSE scores 7 vs. 7.3; p = 0.030). We conclude that AAI in mTBI represents a characteristically different group, which has implications for prevention measures, as well as the course of recovery. PMID:26230219

  19. Acute Alcohol Action and Desensitization of Ligand-Gated Ion Channels

    PubMed Central

    Dopico, Alex M.; Lovinger, David M.

    2009-01-01

    Ethanol exerts its biological actions through multiple receptors, including ion channels. Ion channels that are sensitive to pharmacologically relevant ethanol concentrations constitute a heterogeneous set, including structurally unrelated proteins solely sharing the property that their gating is regulated by a ligand(s). Receptor desensitization is almost universal among these channels, and its modulation by ethanol may be a crucial aspect of alcohol pharmacology and effects in the body. We review the evidence documenting interactions between ethanol and ionotropic receptor desensitization, and the contribution of this interaction to overall ethanol action on channel function. In some cases, such as type 3 serotonin, nicotinic acetylcholine, GABA-A, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, ethanol actions on apparent desensitization play a significant role in acute drug action on receptor function. In a few cases, mutagenesis helped to identify different areas within a receptor protein that differentially sense n-alcohols, resulting in differential modulation of receptor desensitization. However, desensitization of a receptor is linked to a variety of biochemical processes that may alter protein conformation, such as the lipid microenvironment, post-translational channel modification, and channel subunit composition, the relative contribution of these processes to ethanol interactions with channel desensitization remains unclear. Understanding interactions between ethanol and ionotropic receptor desensitization may help to explain different ethanol actions 1) when ethanol is evaluated in vitro on cloned channel proteins, 2) under physiological or pathological conditions or in distinct cell domains with modified ligand concentration and/or receptor conformation. Finally, receptor desensitization is likely to participate in molecular and, possibly, behavioral tolerance to ethanol, which is thought to contribute to the risk of alcoholism. PMID:19270242

  20. iTRAQ-based proteomic analysis of hepatic tissues from patients with hepatitis B virus-induced acute-on-chronic liver failure

    PubMed Central

    PENG, LIANG; LIU, JING; LI, YANG-MEI; HUANG, ZHAN-LIAN; WANG, PEI-PEI; ZHENG, YU-BAO; HUA, YUN-PENG; GAO, ZHI-LIANG

    2015-01-01

    The pathogenesis of hepatitis B virus (HBV)-induced acute-on-chronic liver failure (ACLF), a serious and prevalent medical condition, is not clear, particularly with regard to which proteins are expressed in the course of the disease. The aim of the present study was to identify the differences in hepatic tissue protein expression between normal human subjects and patients with ACLF using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis and to verify the results using western blot analysis. The iTRAQ method was used to analyze the protein contents of hepatic tissue samples from 3 patients with HBV-induced ACLF and 3 normal healthy subjects. The results were verified by subjecting the hepatic tissues from 2 patients with HBV-induced ACLF and 4 healthy subjects to western blot analysis. In total, 57 proteins with ≥1.5-fold differences between patients with HBV-induced ACLF and healthy subjects were identified using iTRAQ. Among these 57 proteins, 4 with the most marked differences in their expression and the most significant association with liver disease were selected to be verified through western blot analysis: Keratin, type-I cytoskeletal 19; α-1-acid glycoprotein 1 (α1-AGP); carbonic anhydrase-1; and serpin peptidase inhibitor and clade A (α-1 anti proteinase, antitrypsin) member 1 (SERPINA1). The results of the western blot analyses were nearly identical to the iTRAQ results. Identifying the differences in liver protein expression in patients with HBV-induced ACLF may provide a basis for studies on the pathogenesis of ACLF. Future studies should focus particularly on α1-AGP, carbonic anhydrase 1 and SERPINA1. PMID:26640544

  1. In vitro inactivation of hepatic alcohol dehydrogenase and aldehyde dehydrogenases from rats by dithiocarbamates with or without metals

    SciTech Connect

    Freundt, K.J.; Schreiner, E.

    1988-10-01

    Alcohol dehydrogenases is localized mainly in the hepatic cytoplasm. Aldehyde dehydrogenases are bound predominantly to the hepatic mitochondrial and endoplasmic reticular membranes; a small part of their total activity is measured in the cytosol. ALDH catalyses the oxidation of acetaldehyde to acetic acid and the metabolism of endogenous or exogenous aldehydes. The goal of the present investigation was to examine in vitro the possible interaction of metal containing dithiocarbamates with the activity of ALDH isolated from rat livers in comparison with that of dithiocarbamates without metals. In addition, the elucidation of an inhibitory effect on isolated liver ADH possibly caused by dithiocarbamates with or without metals could help to explain a previously found delay of ethanol elimination from rat blood. To this end the following substances were tested: The dimers TMTD and TETD, the monomers dimethyldithiocarbamate (DMDC) as sodium salt or as zinc salt and diethyldithiocarbamate (DEDC) as sodium salt, as well as the related compounds tetramethylthiuram monosulfide (TMTM), manganese(II)-(N,N'-ethylenebis(dithiocarbamate)), and zinc-(N,N'-ethylenebis(dithiocarbamate)).

  2. TRC8 downregulation contributes to the development of non-alcoholic steatohepatitis by exacerbating hepatic endoplasmic reticulum stress.

    PubMed

    Chang, Po-Chiao; Tsai, Hung-Wen; Chiang, Ming-Tsai; Huang, Pei-Ling; Shyue, Song-Kun; Chau, Lee-Young

    2015-11-01

    Endoplasmic reticulum (ER) stress is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). TRC8 is an ER-resident E3 ligase with roles in modulating lipid and protein biosynthesis. In this study we showed that TRC8 expression was downregulated in steatotic livers of patients and mice fed with a high fat diet (HFD) or a methionine and choline deficient (MCD) diet. To investigate the impact of TRC8 downregulation on steatosis and the progression to non-alcoholic steatohepatitis (NASH), we placed TRC8 knockout (KO) mice and wild type (WT) controls on a HFD or MCD diet and the severities of steatosis and NASH developed were compared. We found that TRC8 deficiency did not significantly affect diet-induced steatosis. Nevertheless, MCD diet-induced NASH as characterized by hepatocyte death, inflammation and fibrosis were exacerbated in TRC8-KO mice. The hepatic ER stress response, as evidenced by increased eIF2α phosphorylation and expression of ATF4 and CHOP, and the level of activated caspase 3, an apoptosis indicator, were augmented by TRC8 deficiency. The hepatic ER stress and NASH induced in mice could be ameliorated by adenovirus-mediated hepatic TRC8 overexpression. Mechanistically, we found that TRC8 deficiency augmented lipotoxic-stress-induced unfolded protein response in hepatocytes by attenuating the arrest of protein translation and the misfolded protein degradation. These findings disclose a crucial role of TRC8 in the maintenance of ER protein homeostasis and its downregulation in steatotic liver contributes to the progression of NAFLD. PMID:26319415

  3. Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model

    PubMed Central

    Rector, R. Scott; Thyfault, John P.; Uptergrove, Grace M.; Morris, E. Matthew; Naples, Scott P.; Borengasser, Sarah J.; Mikus, Catherine R.; Laye, Matthew J.; Laughlin, M. Harold; Booth, Frank W.; Ibdah, Jamal A.

    2011-01-01

    Background & Aims In this study, we sought to determine the temporal relationship between hepatic mitochondrial dysfunction, hepatic steatosis and insulin resistance, and to examine their potential role in the natural progression of non-alcoholic fatty liver disease (NAFLD) utilising a sedentary, hyperphagic, obese, Otsuka Long–Evans Tokushima Fatty (OLETF) rat model. Methods OLETF rats and their non-hyperphagic control Long–Evans Tokushima Otsuka (LETO) rats were sacrificed at 5, 8, 13, 20, and 40 weeks of age (n = 6–8 per group). Results At 5 weeks of age, serum insulin and glucose and hepatic triglyceride (TG) concentrations did not differ between animal groups; however, OLETF animals displayed significant (p < 0.01) hepatic mitochondrial dysfunction as measured by reduced hepatic carnitine palmitoyl-CoA transferase-1 activity, fatty acid oxidation, and cytochrome c protein content compared with LETO rats. Hepatic TG levels were significantly elevated by 8 weeks of age, and insulin resistance developed by 13 weeks in the OLETF rats. NAFLD progressively worsened to include hepatocyte ballooning, perivenular fibrosis, 2.5-fold increase in serum ALT, hepatic mitochondrial ultrastructural abnormalities, and increased hepatic oxidative stress in the OLETF animals at later ages. Measures of hepatic mitochondrial content and function including β-hydroxyacyl-CoA dehydrogenase activity, citrate synthase activity, and immunofluorescence staining for mitochondrial carbamoyl phosphate synthetase-1, progressively worsened and were significantly reduced at 40 weeks in OLETF rats compared to LETO animals. Conclusions Our study documents that hepatic mitochondrial dysfunction precedes the development of NAFLD and insulin resistance in the OLETF rats. This evidence suggests that progressive mitochondrial dysfunction contributes to the natural history of obesity-associated NAFLD. PMID:20347174

  4. Dialysis-requiring acute kidney injury among hospitalized adults with documented hepatitis C Virus infection: a nationwide inpatient sample analysis.

    PubMed

    Nadkarni, G N; Patel, A; Simoes, P K; Yacoub, R; Annapureddy, N; Kamat, S; Konstantinidis, I; Perumalswami, P; Branch, A; Coca, S G; Wyatt, C M

    2016-01-01

    Chronic hepatitis C virus (HCV) infection may cause kidney injury, particularly in the setting of cryoglobulinemia or cirrhosis; however, few studies have evaluated the epidemiology of acute kidney injury in patients with HCV. We aimed to describe national temporal trends of incidence and impact of severe acute kidney injury (AKI) requiring renal replacement 'dialysis-requiring AKI' in hospitalized adults with HCV. We extracted our study cohort from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project using data from 2004 to 2012. We defined HCV and dialysis-requiring acute kidney injury based on previously validated ICD-9-CM codes. We analysed temporal changes in the proportion of hospitalizations complicated by dialysis-requiring AKI and utilized survey multivariable logistic regression models to estimate its impact on in-hospital mortality. We identified a total of 4 603 718 adult hospitalizations with an associated diagnosis of HCV from 2004 to 2012, of which 51 434 (1.12%) were complicated by dialysis-requiring acute kidney injury. The proportion of hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly from 0.86% in 2004 to 1.28% in 2012. In-hospital mortality was significantly higher in hospitalizations complicated by dialysis-requiring acute kidney injury vs those without (27.38% vs 2.95%; adjusted odds ratio: 2.09; 95% confidence interval: 1.74-2.51). The proportion of HCV hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly between 2004 and 2012. Similar to observations in the general population, dialysis-requiring acute kidney injury was associated with a twofold increase in odds of in-hospital mortality in adults with HCV. These results highlight the burden of acute kidney injury in hospitalized adults with HCV infection. PMID:26189719

  5. Endovascular Treatment of Acute Arterial Hemorrhage in Trauma Patients Using Ethylene Vinyl Alcohol Copolymer (Onyx)

    SciTech Connect

    Mueller-Wille, R. Heiss, P.; Herold, T.; Jung, E. M. Schreyer, A. G. Hamer, O. W. Rennert, J. Hoffstetter, P. Stroszczynski, C.; Zorger, N.

    2012-02-15

    Purpose: This study was designed to determine the feasibility and efficacy of endovascular embolization with liquid embolic agent ethylene vinyl alcohol copolymer (Onyx) in patients with acute traumatic arterial bleeding. Methods: This is a retrospective review of 13 patients (9 men and 4 women; mean age 45 years) with severe trauma who underwent embolotherapy using Onyx from November 2003 to February 2009. Bleeding was located in the pelvis (5 patients), kidney (3 patients), mesenteric region (2 patients), retroperitoneal space (2 patients), neck (1 patient), and thigh (1 patient). In three cases (23.1%), Onyx was used in conjunction with coils. We evaluate the technical and clinical success, procedural and embolization time, occurrence of rebleeding, and embolotherapy-related complications, such as necrosis or migration of Onyx into nontarget vessels. Results: In all patients, embolotherapy was technically and clinically successful on the first attempt. Control of bleeding could be reached with a mean time of 19 (range, 4-63) min after correct placement of the microcatheter in the feeding artery. No recurrent bleeding was detected. No unintended necrosis or migration of Onyx into a nontarget region was observed. During the follow-up period, three patients (23.1%) died due to severe intracranial hemorrhage, cardiac arrest, and sepsis. Conclusions: Transcatheter embolization with new liquid embolic agent Onyx is technically feasible and effective in trauma patients with acute arterial hemorrhage.

  6. Modulatory effect of pineapple peel extract on lipid peroxidation, catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats

    PubMed Central

    Okafor, OY; Erukainure, OL; Ajiboye, JA; Adejobi, RO; Owolabi, FO; Kosoko, SB

    2011-01-01

    Objective To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma. Methods Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3 000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations. Results Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities. Conclusions The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity. PMID:23569717

  7. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats.

    PubMed

    Zhong, Wei; Li, Qiong; Zhang, Wenliang; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2015-01-01

    Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation. PMID:26501337

  8. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

    PubMed Central

    Zhong, Wei; Li, Qiong; Zhang, Wenliang; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2015-01-01

    Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation. PMID:26501337

  9. Delta agent infection in acute hepatitis and chronic HBsAg carriers with and without liver disease.

    PubMed Central

    Crax, A; Raimondo, G; Longo, G; Giannuoli, G; De Pasquale, R; Caltagirone, M; Patti, S; Squadrito, G; Pagliaro, L

    1984-01-01

    Hepatitis B virus (HBV) is a major cause of chronic liver disease in southern Italy. In the same area superinfection with the delta agent is endemic. To assess the prevalence of delta infection in a large population of patients with acute and chronic HBV related liver disease and to look for differential features among delta infected and uninfected subjects sera from 592 consecutive HBsAg positive patients were tested for the delta/anti-delta system by RIA. In no case was delta Ag found in serum. The prevalence of anti-delta was low in acute hepatitis (6.6%) and in asymptomatic carriers (6.4%) but raised in chronic active hepatitis with or without cirrhosis (52.3%). A decrease in frequency of anti-delta was seen in inactive cirrhosis (38.8%) and in hepatocellular carcinoma (11.9%). A younger mean age of delta-infected subjects was observed in each type of chronic liver disease. Our data confirm that delta agent superinfection is definitely associated with severe chronic active liver disease. The difference in age between anti-delta positive and negative patients suggests that delta infection accelerates the natural history of HBV related liver disease. PMID:6500367

  10. Acute alcohol tolerance is intrinsic to the BKCa protein, but is modulated by the lipid environment.

    PubMed

    Yuan, Chunbo; O'Connell, Robert J; Wilson, Andrew; Pietrzykowski, Andrzej Z; Treistman, Steven N

    2008-02-22

    Ethanol tolerance, in which exposure leads to reduced sensitivity, is an important component of alcohol abuse and addiction. The molecular mechanisms underlying this process remain poorly understood. The BKCa channel plays a central role in the behavioral response to ethanol in Caenorhabditis elegans (Davies, A. G., Pierce-Shimomura, J. T., Kim, H., VanHoven, M. K., Thiele, T. R., Bonci, A., Bargmann, C. I., and McIntire, S. L. (2003) Cell 115, 655-666) and Drosophila (Cowmeadow, R. B., Krishnan, H. R., and Atkinson, N. S. (2005) Alcohol. Clin. Exp. Res. 29, 1777-1786) . In neurons, ethanol tolerance in BKCa channels has two components: a reduced number of membrane channels and decreased potentiation of the remaining channels (Pietrzykowski, A. Z., Martin, G. E., Puig, S. I., Knott, T. K., Lemos, J. R., and Treistman, S. N. (2004) J. Neurosci. 24, 8322-8332) . Here, heterologous expression coupled with planar bilayer techniques examines two additional aspects of tolerance in human BKCa channels. 1) Is acute tolerance observed in a single channel protein complex within a lipid environment reduced to only two lipids? 2) Does lipid bilayer composition affect the appearance of acute tolerance? We found that tolerance was observable in BKCa channels in membrane patches pulled from HEK cells and when they are placed into reconstituted 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine membranes. Furthermore, altering bilayer thickness by incorporating the channel into lipid mixtures of 1,2-dioleoyl-3-phosphatidylethanolamine with phosphatidylcholines of increasing chain length, or with sphingomyelin, strongly affected the sensitivity of the channel, as well as the time course of the acute response. Ethanol sensitivity changed from a strong potentiation in thin bilayers to inhibition in thick sphingomyelin/1,2-dioleoyl-3-phosphatidylethanolamine bilayers. Thus, tolerance can be an intrinsic property of the channel protein-lipid complex, and bilayer thickness plays an important role in shaping the pattern of response to ethanol. As a consequence of these findings the protein-lipid complex should be treated as a unit when studying ethanol action. PMID:18084004

  11. Anthocyanins attenuate alcohol-induced hepatic injury by inhibiting pro-inflammation signalling.

    PubMed

    Jiang, Zhihui; Chen, Chen; Xie, Wenyan; Wang, Meng; Wang, Jian; Zhang, Xiaoying

    2016-02-01

    We assessed phytochemical components of anthocyanins from purple sweet potato (PSP) and purple potato (PP) with UPLC-MS/MS, and investigated their inhibitory effect on inflammatory response in alcoholic liver disease (ALD). Results showed that serum AST and ALT levels in PP anthocyanins (PPAs) and PSP anthocyanins (PSPAs) treatments were lower than those of alcohol-treated group. PPAs and PSPAs could inhibit mRNA expressions of inflammatory factors (TNF-α, VCAM-1, IFN-γ and CXCL-1). The mRNA levels of NF-κB, STAT, and TLR in PPAs and PSPAs treatment groups were lower than in alcohol treatment group. Our results indicate that PP and PSP are good source of anti-inflammatory anthocyanins to prevent ALD. PMID:25774691

  12. Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma

    PubMed Central

    Washburn, Shannon E.; Sawant, Onkar B.; Lunde, Emilie R.; Wu, Guoyao; Cudd, Timothy A.

    2013-01-01

    Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21–30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model. PMID:23315157

  13. Acute cold- and chronic heat-exposure upregulate hepatic leptin and muscle uncoupling protein (UCP) gene expression in broiler chickens.

    PubMed

    Dridi, Sami; Temim, Soraya; Derouet, Michel; Tesseraud, Sophie; Taouis, Mohammed

    2008-08-01

    Emerging evidence showed that variations in environmental temperature affect both leptin and uncoupling protein (UCP) gene expression in mammals, whereas a little is known about such interactions in birds. Thus, we conducted the present study to investigate the influence of acute (2 hours) cold (4 degrees C) and chronic (10 days) heat (32 degrees C) exposure on hepatic leptin and muscle UCP gene expression in 5-wk-old broiler chickens. Both cold- and heat-exposure significantly (P < 0.05 to P < 0.001) upregulated hepatic leptin (by 35 and 46%, respectively) and muscle UCP mRNA levels (by 71 and 71%, respectively) compared to the thermoneutrality (22 degrees C). This result suggests that leptin and UCP may be involved in the thermoregulation response of chickens to extreme climate (cold and hot temperatures). The upregulation of hepatic leptin gene expression was accompanied by an increase in plasma leptin levels, indicating that leptin may be regulated at transcriptional level. The increase of leptin and UCP mRNA abundance, and leptinemia we report here were not related to plasma glucose or insulin levels. In conclusion, the exposure of broiler chickens to extreme ambient temperatures (cold and heat) increases hepatic leptin and muscle UCP gene expression. PMID:18473347

  14. [Early liver damage caused by alcohol].

    PubMed

    Garcá Vigil, J L; Aguirre García, J; Pérez Muñoz, H A; López Bárcena, J J; Lifshitz Guinzberg, A

    1980-01-01

    Liver biopsy was taken from 20 patients with chronic and acute alcoholism. The patients had been hospitalized for diverse reasons, had no clinical manifestations of alcoholic hepatitis nor cirrhosis, but did have abnormal liver function tests. The most common abnormal test results were low serum albumin, polyclonal gamma-globulin elevation, and S G O T and Alk P rise. In all patients one or more types of hepatic lesiones were found: steatosis (15), polynuclear and mononuclear infiltrates (15), and portal (7), interstitial (13), or centriobular (8) fibrosis. Two patients had cirrhosis. None had hepatic cell necrosis. These findings justify a motivated search for liver damage in patients with alcoholism who have slight alterations in liver function tests, even in the absence of clinical manifestations of liver disease. PMID:7466143

  15. Cerebral Venous Thrombosis as an Extrahepatic Manifestation of Acute Anicteric Hepatitis A Infection

    PubMed Central

    Zis, Panagiotis; Kontogeorgi, Elli; Karakalos, Dimitrios; Pavlopoulou, Despoina; Sevastianos, Vassilios A.

    2012-01-01

    Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis has been regarded as a rare associated condition. We report the case of a 31-year-old woman presenting with CVT associated with hepatitis A virus (HAV) infection, outlining probable pathogenic mechanisms. We suggest that hepatitis A serological markers should be routinely included in the investigation of cerebral venous thrombosis of unknown etiology, in nonvaccinated patients with risk factors of a recent HAV exposure. PMID:22934203

  16. Hepatic alteration of tryptophan metabolism in an acute porphyria model Its relation with gluconeogenic blockage.

    PubMed

    Lelli, Sandra M; Mazzetti, Marta B; San Martín de Viale, Leonor C

    2008-02-01

    This study focuses on the alterations suffered by the serotoninergic and kinurenergic routes of tryptophan (TRP) metabolism in liver, and their relation with gluconeogenic phosphoenolpyruvate-carboxykinase (PEPCK) blockage in experimental acute porphyria. This porphyria was induced in rats by a combined treatment of 2-allyl-2-isopropylacetamide (100, 250, 500 mg/kg bw) and 3,5-dietoxicarbonil 1,4-dihydrocollidine (constant 50 mg/kg bw dose). Results showed a marked dose-dependent increase of all TRP pyrrolase (TRPp) forms, active (holo, total) and inactive (apo), and a decrease in the degree of enzyme saturation by heme. Increases for holo, total, and apo-TRPp were 90, 150, and 230%, respectively, at the highest dose assayed (H). The treatment also impaired the serotoninergic route of TRP metabolism in liver, causing a decrease in serotonin level (H, 38%), and a concomitant enhancement in TRP content (H, 23%). The porphyrinogenic treatment promoted a blockage in PEPCK activity (H, 30%). This occurred in correlation to the development of porphyria, to TRPp alterations and to the production of hepatic microsomal thiobarbituric acid reactive substances. Porphyria was estimated through increases in 5-aminolevulinic acid-synthase (ALA-S) activity, ALA and porphobilinogen contents, and a decrease in ferrochelatase activity. Thus, the TRP kynurenine route was augmented whereas the serotoninergic route was reduced. PEPCK blockage could be partly attributed to quinolinate generated from TRP by the increase of TRPp activity, which would be due to the effect of porphyrinogenic drugs on TRP. The contribution of ROS to PEPCK blockage is analyzed. Likewise, the implication of these results in the control of porphyrias by glucose is discussed. PMID:17996218

  17. Traumatic Life Events Prior to Alcohol-Related Admission of Injured Acute Care Inpatients: A Brief Report

    PubMed Central

    Peterson, Roselyn; Russo, Joan; Darnell, Doyanne; Wang, Jin; Ingraham, Leah; Zatzick, Douglas

    2016-01-01

    Objective Approximately 30 million Americans present to acute care medical settings annually after incurring traumatic injuries. Posttraumatic stress disorder and depressive symptoms are endemic among injury survivors. Our paper is a replication and extension of a previous report documenting a pattern of multiple traumatic life events across patients admitted to Level I trauma centers for an alcohol-related injury. Method This study is a secondary analysis of a nationwide 20-site randomized trial of an alcohol brief intervention with 660 traumatically injured inpatients. Pre-injury trauma history was assessed using the National Comorbidity Survey trauma history screen at the 6 month time point. Results Most common traumatic events experienced by our population of alcohol positive trauma survivors were having had someone close unexpectedly die, followed by having seen someone badly beaten or injured. Of particular note, there is high reported prevalence of rape/sexual assault, and childhood abuse and neglect among physically injured trauma survivors. Additional trauma histories are increasingly common among alcohol-positive patients admitted for a traumatic injury. Conclusions Due to the high rate of experienced multiple traumatic events among acutely injured inpatients, the trauma history screen could be productively integrated into screening and brief intervention procedures developed for acute care settings. PMID:26745689

  18. Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

    PubMed Central

    El-Diwany, Ramy; Wasilewski, Lisa N.; Witwer, Kenneth W.; Bailey, Justin R.; Page, Kimberly; Ray, Stuart C.; Cox, Andrea L.; Thomas, David L.

    2015-01-01

    ABSTRACT Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (Pcorrected < 0.05) and a decrease in miR-494 (Pcorrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCE MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe liver disease. We profiled plasma miRNAs in injection drug users before, during, and (in the people with resolution) after HCV infection. We discovered miRNA signatures of acute and persistent viremia and confirmed these findings two ways: (i) in a separate cohort of people with newly acquired HCV infection and (ii) in an HCV cell culture system. Our results demonstrate that acute HCV infection induces early changes in the abundance of specific plasma miRNAs that may affect the host response to HCV infection. PMID:26157120

  19. Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice.

    PubMed

    Wang, Meng; You, Qiang; Lor, Kenton; Chen, Fangfang; Gao, Bin; Ju, Cynthia

    2014-10-01

    Hepatic Macs, consisting of resident KCs and infiltrating monocytes/IMs, are thought to play an important role in the pathogenesis of ALD. Previous work has focused on KCs or studied hepatic Macs as one cell population. The aim of the current study is to distinguish IMs from KCs and to compare their phenotypes and functions. We show here that a 4-week ethanol feeding of C57BL/6J mice causes recruitment of IMs into the liver. KCs and IMs can be distinguished based on their differential expression of F4/80 and CD11b. IMs can be divided further into two subsets based on their differential expression of Ly6C. KCs and two subsets of IMs were separately purified by FACS. The phagocytosis abilities and the expression profiles of genes related to various functions were compared among different populations of hepatic Macs. Ly6C(low) IMs exhibit an anti-inflammatory and tissue-protective phenotype; in contrast, Ly6C(hi) IMs exhibit a proinflammatory, tissue-damaging phenotype. The ratio of Ly6C(hi)/Ly6C(low) increases when mice chronically fed ethanol were binged, which significantly enhanced liver injury. Moreover, upon phagocytosis of apoptotic hepatocytes, Ly6C(hi) IMs switch to Ly6C(low) IMs. Taken together, chronic ethanol feeding induces the recruitment of two subsets of hepatic IMs, which play different or even opposite roles in regulating liver inflammation and repair. These findings may not only increase our understanding of the complex functions of Macs in the pathogenesis of ALD but also help us to identify novel therapeutic targets for the treatment of this disease. PMID:25030420

  20. PPARδ agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair

    PubMed Central

    Pang, Maoyin; de la Monte, Suzanne M.; Longato, Lisa; Tong, Ming; He, Jiman; Chaudhry, Rajeeve; Duan, Kevin; Ouh, Jiyun; Wands, Jack R.

    2009-01-01

    Background/Aims Chronic ethanol exposure impairs liver regeneration due to inhibition of insulin signaling and oxidative injury. PPAR agonists function as insulin sensitizers and anti-inflammatory agents. We investigated whether treatment with a PPARδ agonist could restore hepatic insulin sensitivity, survival signaling, and regenerative responses vis-a-vis chronic ethanol feeding. Methods Adult rats were fed isocaloric liquid diets containing 0% or 37% ethanol, and administered a PPARδ agonist by i.p. injection. We used liver tissue to examine histopathology, gene expression, oxidative stress, insulin signaling, and regenerative responses to 2/3 hepatectomy. Results Chronic ethanol feeding caused insulin resistance, increased oxidative stress, lipid peroxidation, DNA damage, and hepatocellular injury in liver. These effects were associated with reduced insulin receptor binding and affinity, impaired survival signaling through PI3K/Akt/GSK3β, and reduced expression of insulin responsive genes mediating energy metabolism and tissue remodeling. PPARδ agonist treatment reduced ethanol-mediated hepatic injury, oxidative stress, lipid peroxidation, and insulin resistance, increased signaling through PI3K/Akt/GSK3β, and enhanced the regenerative response to partial hepatectomy. Conclusions PPARδ agonist administration may attenuate the severity of chronic ethanol-induced liver injury and ethanol’s adverse effects on the hepatic repair by restoring insulin responsiveness, even in the context of continued high-level ethanol consumption. PMID:19398227

  1. Effects of low-level light therapy on hepatic antioxidant defense in acute and chronic diabetic rats.

    PubMed

    Lim, Jinhwan; Ali, Zeeshan M; Sanders, Ruth A; Snyder, Ann C; Eells, Janis T; Henshel, Diane S; Watkins, John B

    2009-01-01

    Diabetes causes oxidative stress in the liver and other tissues prone to complications. Photobiomodulation by near infrared light (670 nm) has been shown to accelerate diabetic wound healing, improve recovery from oxidative injury in the kidney, and attenuate degeneration in retina and optic nerve. The present study tested the hypothesis that 670 nm photobiomodulation, a low-level light therapy, would attenuate oxidative stress and enhance the antioxidant protection system in the liver of a model of type I diabetes. Male Wistar rats were made diabetic with streptozotocin (50 mg/kg, ip) then exposed to 670 nm light (9 J/cm(2)) once per day for 18 days (acute) or 14 weeks (chronic). Livers were harvested, flash frozen, and then assayed for markers of oxidative stress. Light treatment was ineffective as an antioxidant therapy in chronic diabetes, but light treatment for 18 days in acutely diabetic rats resulted in the normalization of hepatic glutathione reductase and superoxide dismutase activities and a significant increase in glutathione peroxidase and glutathione-S transferase activities. The results of this study suggest that 670 nm photobiomodulation may reduce, at least in part, acute hepatic oxidative stress by enhancing the antioxidant defense system in the diabetic rat model. PMID:19202557

  2. Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer.

    PubMed Central

    Fearon, K C; McMillan, D C; Preston, T; Winstanley, F P; Cruickshank, A M; Shenkin, A

    1991-01-01

    It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation. PMID:1898691

  3. Application of an alcohol clamp paradigm to examine inhibitory control, subjective responses, and acute tolerance in late adolescence.

    PubMed

    Hendershot, Christian S; Wardell, Jeffrey D; Strang, Nicole M; Markovich, Mike S D; Claus, Eric D; Ramchandani, Vijay A

    2015-06-01

    Individual differences in acute alcohol effects on cognitive control and subjective responses--and acute tolerance to these effects--are implicated in the risk for heavy drinking and alcohol-related harms. Few studies have examined these effects in drinkers under age 21. Additionally, studies of acute tolerance typically involve bolus oral alcohol administration, such that estimates of tolerance are confounded with blood alcohol concentration (BAC) limb. The current study examined cognitive control and subjective responses in young heavy drinkers (n = 88; M = 19.8 years old, SD = 0.8) during a single-session alcohol clamp protocol. Participants completed an intravenous alcohol session comprising an ascending limb (0 to 80 mg% in 20 min) and a BAC plateau (80 mg% for 80 min). Serial assessments included a cued go/no-go task and measures of stimulation, sedation, and craving. Relevant individual difference factors (attention-deficit hyperactivity disorder [ADHD] symptoms and sensation seeking) were examined as moderators. Multilevel modeling demonstrated that response inhibition worsened following initial rise in BAC and showed increasing impairment during the BAC plateau. ADHD symptoms and sensation seeking moderated this effect. Significant within-person associations between stimulation and craving were evident on the ascending limb only. Participants with higher ADHD symptoms reported steeper increases in stimulation during the ascending limb. These findings provide initial information about subjective and behavioral responses during pseudoconstant BAC, and potential moderators of these outcomes, in late adolescence. Additional studies with placebo-controlled designs are necessary to confirm these findings. PMID:26053322

  4. Effect of alcohol on hepatic receptor of high density lipoproteins (HDL)

    SciTech Connect

    Lin, R.C.; Miller, B.M. V.A. Medical Center, Indianapolis, IN )

    1991-03-11

    Moderate alcohol intake has been shown to increase HDL cholesterol and proteins. The seemingly protective effect' of moderate alcohol drinking against cardiovascular diseases has been attributed to an increase in serum HDL. In this study, the authors show that a receptor for HDL is present in rat liver. Rat liver membrane was prepared by stepwise ultracentrifugation. Apo Al was iodinated using {sup 125}I-NaI and IODO-beads. HDL was labeled by incubating with {sup 125}I-apo Al then refloated be centrifugation. Binding of {sup 125}I-HDL to rat liver membrane reached equilibrium by 2-3 h and was saturable at 37C. The binding was inhibited 80% by excess unlabeled HDL, but was inhibited only 25% by excess LDL. It could also be inhibited by preincubating HDL with anti-apo Al or anti-apo E antisera but not with anti-apo AIV or control sera. The binding affinity of HDL to the liver membrane of rats fed alcohol for 5 wk was 50% that of their pair-fed controls. Thus a decrease in the binding of HDL to liver membrane due to alcohol-drinking may result in a slower clearance of HDL by the liver and consequently a higher HDL concentration in the serum.

  5. Brief motivational intervention for adolescents treated in emergency departments for acute alcohol intoxication – a randomized-controlled trial

    PubMed Central

    2014-01-01

    Background Alcohol misuse among youth is a major public health concern and numbers of adolescents admitted to the emergency department for acute alcoholic intoxication in Germany are recently growing. The emergency setting offers an opportunity to reach at-risk alcohol consuming adolescents and provide brief interventions in a potential “teachable moment”. However, studies on brief interventions targeting adolescents in emergency care are scarce and little is known about their effectiveness when delivered immediately following hospitalization for acute alcohol intoxication. In this protocol we present the HaLT-Hamburg trial evaluating a brief motivational intervention for adolescents treated in the emergency department after an episode of acute alcoholic intoxication. Methods The trial design is a parallel two-arm cluster randomized-controlled trial with follow-up assessment after 3 and 6 months. N = 312 participants aged 17 years and younger will be recruited Fridays to Sundays in 6 pediatric clinics over a period of 30 months. Intervention condition is a manual-based brief motivational intervention with a telephone booster after 6 weeks and a manual-guided intervention for caregivers which will be compared to treatment as usual. Primary outcomes are reduction in binge drinking episodes, quantity of alcohol use on a typical drinking day and alcohol-related problems. Secondary outcome is further treatment seeking. Linear mixed models adjusted for baseline differences will be conducted according to intention-to-treat (ITT) and completers (per-protocol) principles to examine intervention effects. We also examine quantitative and qualitative process data on feasibility, intervention delivery, implementation and receipt from intervention providers, receivers and regular emergency department staff. Discussion The study has a number of strengths. First, a rigorous evaluation of HaLT-Hamburg is timely because variations of the HaLT project are widely used in Germany. Second, prior research has not targeted adolescents in the presumed teachable moment following acute alcohol intoxication. Third, we included a comprehensive process evaluation to raise external validity. Fourth, the study involved important stakeholders from the start to set up organizational structures for implementation and maintaining project impact. Trial registration Current Controlled Trials ISRCTN31234060 (April 30th 2012). PMID:24975110

  6. Acute, fatal Sarcocystis calchasi-associated hepatitis in Roller pigeons (Columba livia f. dom.) at Philadelphia Zoo.

    PubMed

    Trupkiewicz, J G; Calero-Bernal, R; Verma, S K; Mowery, J; Davison, S; Habecker, P; Georoff, T A; Ialeggio, D M; Dubey, J P

    2016-01-30

    Four Roller pigeons (Columba livia f. dom.) at the Philadelphia Zoo died suddenly. Necropsy examination revealed macroscopic hepatitis. Microscopically, the predominant lesions were in liver, characterized with necrosis and mixed cell inflammatory response. Sarcocystis calchasi-like schizonts and free merozoites were identified in liver. Transmission electron microscopy confirmed that schizonts were in hepatocytes. A few schizonts were in spleen. PCR using S. calchasi-specific primers confirmed the diagnosis. Neither lesions nor protozoa were found in brain and muscles. This is the first report of acute visceral S. calchasi-associated sarcocystosis in naturally infected avian hosts. PMID:26801595

  7. [Efficacy of application of thiopoietines in complex of treatment of an acute adhesive ileus in patients with hepatic function disorder].

    PubMed

    Vansovych, V Ie; Il'ïna-Stogniienko, V Iu

    2012-11-01

    The peculiarities of an acute adhesive ileus (AAI) course in patients, suffering hepatic function disorder (HFD), were studied up, the additions to the conservative treatment scheme were proposed. There was established, that while HFD presence in the patients the trustworthy enhanced recurrence rate of adhesive disease is observed after operations, performed for AAM, The adhesive disease recurrence rate do not depend on the surgical access kind. Application of preparations, related to thiopoietins group and hepatoprotectors, while AAI treatment conduction, have promoted reduction of the peritoneal adhesive disease recurrence rate in terms of the three years postoperative follow-up. PMID:23272389

  8. Acute Alcohol Intoxication Prolongs Neuroinflammation without Exacerbating Neurobehavioral Dysfunction following Mild Traumatic Brain Injury

    PubMed Central

    Teng, Sophie X.

    2014-01-01

    Abstract Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ?1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5?g/kg+0.3?g/kg/h for 15?h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (?1.4?J, ?30?ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6?h and 24?h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6?h, which was resolved at 24?h. AAI did not modulate the inflammatory response at 6?h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-?, and MCP-1 expression) at 24?h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411

  9. Hepatic Artery and Portal Vein Doppler Indexes in Non-alcoholic Fatty Liver Disease Before and After Treatment to Prevent Unnecessary Health Care Costs

    PubMed Central

    Tarzamni, Mohammad Kazem; Khoshbaten, Manouchehr; Sadrarhami, Shohreh; Daneshpajouhnejad, Parnaz; Jalili, Javad; Gholamian, Masoud; Shahmoradi, Zahra

    2014-01-01

    Background: We tested whether hepatic haemodynamics assessed by Doppler ultrasonography can be a predictor of response to therapy in patients with non-alcoholic fatty liver disease (NAFLD) to prevent further unnecessary diagnostic tests and interventions. Methods: Forty eight consecutive patients affected by NAFLD, who refered to some clinics in Tabriz, Iran between 2009 and 2011 were included in the study. Response to therapy was assessed by decrease in liver enzyme levels. Three liver Doppler parameters (hepatic artery resistance index [RI], hepatic artery pulsatility index [PI] and portal vein waveform [PVW]) were analysed in all subjects who showed a decrease in liver function tests results. Wilcoxon and paired student's t-test were used for analysis. Results: Forty eight subjects with NAFLD were included in the study during 21 months, out of which 22 (39.1% male - mean age: 37.6 ± 8.3) responded to the treatment and formed the basis of this study. Mean hepatic artery RI increased significantly from 0.60 ± 0.07 to 0.83 ± 0.27before and after treatment, however, there was no significant differences between hepatic artery PI or PVW. Conclusions: Increase in hepatic artery RI assessed by Doppler ultrasound may provide information on improvement of NAFLD in patients during the course of therapy. PMID:24829735

  10. Alcohol

    MedlinePlus

    ... years is common. Some reasons that teens use alcohol and other drugs are: curiosity to feel good, reduce stress, and relax to fit in to feel older From a very young age, kids see advertising messages showing beautiful people ...

  11. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  12. Diagnosis of alcoholic cirrhosis with the right-to-left hepatic lobe ratio: concise communication

    SciTech Connect

    Shreiner, D.P.; Barlai-Kovach, M.

    1981-02-01

    Since scans of cirrhotic livers commonly show a reduction in size and colloid uptake of the right lobe, a quantitative measure of uptake was made using a minicomputer to determine total counts in regions of interest defined over each lobe. Right-to-left ratios were then compared in 103 patients. For normal paitents the mean ratio +- 1 s.d. was 2.85 +- 0.65, and the mean for patients with known cirrhosis was 1.08 +- 0.33. Patients with other liver diseases had ratios similar to the normal group. The normal range of the right-to-left lobe ratio was 1.55 to 4.15. The sensitivity of the ratio for alcoholic cirrhosis was 85.7% and the specificity was 100% in this patient population. The right-to-left lobe ratio was more sensitive and specific for alcoholic cirrhosis than any other criterion tested. An hypothesis is described to explain these results.

  13. Hepatic scavenger receptor BI is associated with type 2 diabetes but unrelated to human and murine non-alcoholic fatty liver disease.

    PubMed

    Rein-Fischboeck, Lisa; Krautbauer, Sabrina; Eisinger, Kristina; Pohl, Rebekka; Meier, Elisabeth M; Weiss, Thomas S; Buechler, Christa

    2015-11-13

    Scavenger receptor, class B type I (SR-BI) is a physiologically relevant regulator of high density lipoprotein (HDL) metabolism. Low HDL is a common feature of patients with non-alcoholic fatty liver disease (NAFLD). Here, hepatic SR-BI expression was analyzed in human and murine NAFLD. In primary human hepatocytes NAFLD relevant factors like inflammatory cytokines, lipopolysaccharide and TGF-β did not affect SR-BI protein. Similarly, oleate and palmitate had no effect. The adipokines chemerin, adiponectin, leptin and omentin did not regulate SR-BI expression. Accordingly, hepatic SR-BI was not changed in human and murine fatty liver and non-alcoholic steatohepatits. SR-BI was higher in type 2 diabetes patients but not in those with hypercholesterolemia. The current study indicates a minor if any role of SR-BI in human and murine NAFLD. PMID:26431876

  14. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  15. Hepatic decompensation in the absence of obvious precipitants: the potential role of cytomegalovirus infection/reactivation

    PubMed Central

    Rosi, Silvia; Poretto, Valentina; Cavallin, Marta; Angeli, Paolo; Amodio, Piero; Sattin, Andrea; Montagnese, Sara

    2015-01-01

    Details of two patients with alcohol-related and mixed aetiology cirrhosis who developed acute-on-chronic liver failure/hepatic decompensation with no obvious precipitants are reported. Cytomegalovirus (CMV) infection or reactivation was diagnosed in both, and required treatment with ganciclovir in one. Both returned to baseline hepatic function and remain well. Physicians should be alert to the possibility that CMV might cause or contribute to hepatic decompensation in patients with cirrhosis, even if they are not severely immunocompromised, and especially if they are alcohol misusers. PMID:26629358

  16. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    PubMed

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application. PMID:26617183

  17. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice.

    PubMed

    Ideta, Takayasu; Shirakami, Yohei; Miyazaki, Tsuneyuki; Kochi, Takahiro; Sakai, Hiroyasu; Moriwaki, Hisataka; Shimizu, Masahito

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p < 0.05). Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p < 0.05). Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis. PMID:26670228

  18. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice

    PubMed Central

    Ideta, Takayasu; Shirakami, Yohei; Miyazaki, Tsuneyuki; Kochi, Takahiro; Sakai, Hiroyasu; Moriwaki, Hisataka; Shimizu, Masahito

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p < 0.05). Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p < 0.05). Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis. PMID:26670228

  19. Acute aquatic toxicity of nine alcohol ethoxylate surfactants to fathead minnow and Daphnia magna

    SciTech Connect

    Wong, D.C.L.; Dorn, P.B.; Chai, E.Y.

    1995-12-31

    The aquatic toxicity of nine commercial-grade alcohol ethoxylate surfactants was studied in acute exposures to fathead minnow (Pimephales promelas) and Daphnia magna. All studies were conducted in accordance with USEPA TSCA Good Laboratory Practice Standards. Mean measured surfactant concentrations in exposure solutions showed good agreement with nominal concentrations for both fathead minnow and daphnid tests. Surfactant recoveries ranged from 59 to 97% and 67 to 106% in the fathead minnow and daphnid solutions, respectively. The response of both species to the surfactants was generally similar with the daphnids being slightly more sensitive to a few surfactants. Surfactant toxicity tended to increase with increasing alkyl chain lengths. The effect of low average EO groups on increased surfactant toxicity was more evident in the daphnid exposures. Quantitative structure-activity relationship (QSAR) models were developed form the data which relates surfactant structure to toxicity. The models predict increasing toxicity with decreasing EO number and increasing alkyl chain length. The models also indicate that alkyl chain length has a greater effect on toxicity than EO groups. Further, the models indicate that both species did not differ markedly in their sensitivity to alkyl chain length effects, while the number of EO groups had a stronger effect on daphnids than fathead minnow. Good agreement was found between QSAR model-predicted toxicity and reported toxicity values from the literature for several surfactants previously studied.

  20. Perceived medical risks of drinking, alcohol consumption, and hepatitis C status among heavily drinking HIV primary care patients

    PubMed Central

    Elliott, Jennifer C.; Aharonovich, Efrat; O'Leary, Ann; Johnston, Barbara; Hasin, Deborah S.

    2016-01-01

    BACKGROUND Heavy drinking poses significant risks to the health and survival of individuals infected with HIV, particularly those co-infected with hepatitis C virus (HCV). However, little is known about patients’ perceptions of these risks, and whether these perceptions relate to their alcohol consumption. METHODS A sample of 254 heavily drinking HIV primary care patients (78% male; 94.5% minority; 31.8% with HCV) reported on their perceptions of the medical risks of drinking and on their alcohol consumption prior to participation in a drinking-reduction intervention trial. RESULTS In the HIV-infected sample as a whole, 62.9% reported that they had a medical problem made worse by drinking, and 64.3% reported restricting drinking to avoid future medical problems. Although patients co-infected with HIV/HCV reported greater efforts to restrict drinking to avoid future medical problems (AOR=1.94), their reported drinking quantity and frequency did not differ from that of HIV mono-infected patients. Awareness of medical risk was not associated with drinking level. Effort to restrict drinking to avoid medical risk was associated with lower drinking quantity, frequency, and binge frequency (ps<0.05), but the association with binge frequency was specific to patients without HCV. CONCLUSIONS Over one-third of HIV patients are unaware of the medical risks of drinking, and do not restrict use, suggesting the need for intervention in this group. Patients co-infected with HIV/HCV may report more effort to restrict drinking, but their reported drinking quantity and frequency suggest that they are actually drinking just as heavily as HIV mono-infected patients. Awareness of medical risk was unrelated to drinking, which suggests the need for interventions consisting of more than simple education. However, reported effort to restrict drinking did predict less drinking, suggesting the importance of patient commitment and initiative in change. PMID:25581660

  1. Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice

    PubMed Central

    Rafacho, Bruna Paola Murino; Stice, Camilla Peach; Liu, Chun; Greenberg, Andrew S.; Ausman, Lynne M.

    2015-01-01

    Background Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. Methods C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. Results DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). Conclusions Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway. PMID:26005679

  2. Detection of host immune responses in acute phase sera of spontaneous resolution versus persistent hepatitis C virus infection.

    PubMed

    Selvarajah, Suganya; Keating, Sheila; Heitman, John; Lu, Kai; Simmons, Graham; Norris, Philip J; Operskalski, Eva; Mosley, James W; Busch, Michael P

    2012-08-01

    Prior to the identification of hepatitis C virus (HCV), transfusion-transmission was common. Viral transmission in subjects with a known date of infection allows the study of the immune responses to acute HCV infection. We analysed 39 soluble immune factors in serum samples from subjects with transfusion-transmitted HCV. Dynamic expression kinetics of interferon gamma-induced protein 10 (IP-10), tumour necrosis factor-alpha and interleukin (IL)-10 were observed during acute HCV infection. Serum IP-10 was the only analyte that was significantly elevated in HCV resolvers compared with uninfected controls. In individuals who progressed to chronic HCV elevated levels of IP-10 and IL-10 coincided with first significant alanine aminotransferase elevation and remained elevated during the first year of acute HCV infection. In addition to monitoring lack of reduction in viral load, serum levels of IP-10 and IL-10 expression during acute HCV infection may be useful biomarkers to predict the progress to chronic HCV. PMID:22535775

  3. Hepatic and Nephric NRF2 Pathway Up-Regulation, an Early Antioxidant Response, in Acute Arsenic-Exposed Mice

    PubMed Central

    Li, Jinlong; Duan, Xiaoxu; Dong, Dandan; Zhang, Yang; Li, Wei; Zhao, Lu; Nie, Huifang; Sun, Guifan; Li, Bing

    2015-01-01

    Inorganic arsenic (iAs), a proven human carcinogen, damages biological systems through multiple mechanisms, one of them being reactive oxygen species (ROS) production. NRF2 is a redox-sensitive transcription factor that positively regulates the genes of encoding antioxidant and detoxification enzymes to neutralize ROS. Although NRF2 pathway activation by iAs has been reported in various cell types, however, the experimental data in vivo are very limited and not fully elucidated in humans. The present investigation aimed to explore the hepatic and nephric NRF2 pathway upregulation in acute arsenic-exposed mice in vivo. Our results showed 10 mg/kg NaAsO2 elevated the NRF2 protein and increased the transcription of Nrf2 mRNA, as well as up-regulated NRF2 downstream targets HO-1, GST and GCLC time- and dose-dependently both in the liver and kidney. Acute NaAsO2 exposure also resulted in obvious imbalance of oxidative redox status represented by the increase of GSH and MDA, and the decrease of T-AOC. The present investigation reveals that hepatic and nephric NRF2 pathway expression is an early antioxidant defensive response upon iAs exposure. A better knowledge about the NRF2 pathway involvment in the cellular response against arsenic could help improve the strategies for reducing the cellular toxicity related to this metalloid. PMID:26473898

  4. Protective Effect of Baccharis trimera Extract on Acute Hepatic Injury in a Model of Inflammation Induced by Acetaminophen

    PubMed Central

    Pádua, Bruno da Cruz; Rossoni Júnior, Joamyr Victor; de Brito Magalhães, Cíntia Lopes; Chaves, Míriam Martins; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia; de Souza, Gustavo Henrique Bianco; Brandão, Geraldo Célio; Rodrigues, Ivanildes Vasconcelos; Lima, Wanderson Geraldo; Costa, Daniela Caldeira

    2014-01-01

    Background. Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. Methods. The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. Results. The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. Conclusions. The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose. PMID:25435714

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

    PubMed

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

    2016-01-01

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

  6. In vitro covalent binding of cismethrin, bioresmethrin, and their common alcohol to hepatic proteins

    SciTech Connect

    Hoellinger, H.; Sonnier, M.; Gray, A.J.; Connors, T.A.; Pichon, J.; Nguyen, H.N.

    1985-01-01

    When (/sup 14/C)Alcohol-labeled cismethrin, bioresmethrin, and 5-benzyl-3-furylmethyl alcohol (BFA) were incubated with rat liver S 9 homogenates or microsomes, a proportion of the radioactive compounds was covalently bound to proteins. The covalent binding was greater with phenobarbital-pretreated rats, and dependent on a NADPH-generating system. When a S 9 homogenate was used, the bound compounds were two times higher for cismethrin than for bioresmethrin and BFA. Inversely, when microsomes were used more covalent binding occurred with bioresmethrin and BFA than with cismethrin. The inhibition of esterases by tetraethyl pyrophosphate (TEPP) in a S 9 homogenate did not alter the amount of covalent binding to the three compounds whereas malathion inhibited this binding. Treatment of a S 9 homogenate with piperonyl butoxide, however, greatly reduced covalent binding. Covalent binding was inhibited when the microsomes were incubated with carbon monoxide or modified by thermal denaturation. It is suggested that oxidative metabolism was responsible for the covalent binding.

  7. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Esprito Santo

    PubMed Central

    Gonalves, Patricia Lofego; da Penha Zago-Gomes, Maria; Marques, Carla Couzi; Mendona, Ana Tereza; Gonalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

    2013-01-01

    OBJECTIVES: To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. METHODS: The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. RESULTS: The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.212.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1%), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1%), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (p<0.001) with reduced age (at the time of cirrhosis diagnosis) and increased prevalence of hepatocellular carcinoma (p?=?0.052). CONCLUSION: Alcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis. PMID:23644846

  8. Interferon Lambda 4 Genotype Is Associated With Jaundice and Elevated Aminotransferase Levels During Acute Hepatitis C Virus Infection: Findings From the InC3 Collaborative.

    PubMed

    Page, Kimberly; Mirzazadeh, Ali; Rice, Thomas M; Grebely, Jason; Kim, Arthur Y; Cox, Andrea L; Morris, Meghan D; Hellard, Margaret; Bruneau, Julie; Shoukry, Naglaa H; Dore, Gregory J; Maher, Lisa; Lloyd, Andrew R; Lauer, Georg; Prins, Maria; McGovern, Barbara H

    2016-01-01

    Symptomatic acute HCV infection and interferon lambda 4 (IFNL4) genotypes are important predictors of spontaneous viral clearance. Using data from a multicohort database (Injecting Cohorts [InC3] Collaborative), we establish an independent association between host IFNL4 genotype and symptoms of acute hepatitis C virus infection. This association potentially explain