Sample records for acute alcoholic hepatitis

  1. "Pseudotumoral" hepatic pattern in acute alcoholic hepatitis: a case report.

    PubMed

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

    2009-08-28

    In acute alcoholic hepatitis (AAH), a "pseudotumoral" appearance of the liver parenchyma on computed tomography (CT) scan has been reported. The main findings are hypervascularized areas closely similar to those observed in large hepatocellular carcinomas. We report a case of a patient affected by AAH with an unusual appearance of these "pseudotumoral" areas on CT scan, close resembling a metastatic cancer rather than a primary hepatocellular carcinoma. In fact, in contrast with previous reports, the picture was characterized by the presence of many inhomogeneous, hypoattenuated areas highlighted during both pre- and post-contrast phases. Moreover, we report the first description of "pseudotumoral" lesions on ultrasound scan. This patient was successfully treated with corticosteroids, even if many controversies still exist regarding their efficacy in this setting. PMID:19705506

  2. 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

  3. Prognosis and treatment of patients with acute alcoholic hepatitis.

    PubMed

    Papastergiou, Vassilios; Burroughs, Andrew K; Tsochatzis, Emmanuel A

    2014-07-01

    Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey's discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders. PMID:24716632

  4. Alcoholic hepatitis.

    PubMed

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (< 84 days after diagnosis), patients with AH were likely to die from liver-related events and infections. In the long-term (? 84 days after diagnosis), those who developed cirrhosis mainly died from liver-related causes, and those who did not develop cirrhosis mainly died from causes related to alcohol abuse. In conclusion, the present thesis provides novel warranted epidemiological information about AH that shows increasing incidence and mortality rates. Consequently, it reiterates the fact that AH is a life-threatening disease and suggests that AH is an increasing public health concern. The most widely used prognostic models may be helpful adjuvants in the routine management of patients with AH, provided that clinicians are aware of the models' limitations. The causes of death in AH are primarily due to liver-related complications, suggesting that patients with AH could benefit from continued follow-up by a hepatologist after the acute episode. PMID:25283626

  5. Alcoholic hepatitis: a clinician's guide.

    PubMed

    Choi, Gina; Runyon, Bruce Allen

    2012-05-01

    Alcoholic hepatitis is a frequent reason for admission and a common consultation request for hepatologists and gastroenterologists. Although it seems to occur acutely, it is usually subacute and often superimposed on underlying alcoholic cirrhosis. Typically patients have a background of drinking on a daily basis, but, in response to a life crisis, patients have started drinking massively. PMID:22541704

  6. 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

  7. Management of alcoholic hepatitis: Current concepts

    PubMed Central

    Karsan, Hetal A; Parekh, Samir

    2012-01-01

    Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality. It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role. Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy. Primary therapy remains abstinence and supportive care, as continued alcohol abuse is the most important risk factor for disease progression. The cornerstone of supportive care remains aggressive nutritional support, and although acute alcoholic hepatitis has been extensively studied, few specific medical therapies have been successful. Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis; however, the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary. While liver transplantation for acute alcoholic hepatitis have demonstrated promising results, this practice remains controversial and has not been advocated universally, with most transplant centers requiring a prolonged period of abstinence before considering transplantation. Extracorporeal liver support devices, although still experimental, have been developed as a form of liver support to give additional time for liver regeneration. These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease. PMID:23355911

  8. 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.

  9. Optimal management of alcoholic hepatitis.

    PubMed

    Raff, E; Singal, A K

    2014-03-01

    Alcoholic hepatitis, a clinical syndrome among people with chronic and active alcohol abuse presents with with jaundice and liver failure with or without hepatic encephalopathy. In patients with severe episode, this condition has a potential for 40-50% mortality within a month of presentation. Corticosteroids and pentoxifylline, only available current treatment options provide only about 50% survival benefit. Response to corticosteroids can only be assessed at 1 week of initiation of these drugs using Lille score or documentation of improvement in bilirubin levels. Requirement of minimum 6 months abstinence for liver transplantation cannot be met for alcoholic hepatitis patients who fail to respond to steroids. Emerging data on the benefit of liver transplantation for select patients with first episode of severe AH with non-response to steroids are encouraging. There remains an unmet need for studies assessing newer therapeutic targets and drugs and for optimizing the currently available treatment options. In this regard, decision to promote clinical and translational research by the National Institute of Alcohol Abuse and Alcoholism will be helpful in improving survival of patients with alcoholic hepatitis. PMID:24632766

  10. 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

  11. Acute and chronic alcohol abuse modulate immunity.

    PubMed

    Brown, Lou Ann S; Cook, Robert T; Jerrells, Thomas R; Kolls, Jay K; Nagy, Laura E; Szabo, Gyongyi; Wands, Jack R; Kovacs, Elizabeth J

    2006-09-01

    This article represents the proceedings of the Alcohol and Immunology Research Interest Group (AIRIG) meeting, a satellite workshop held at the 37th Annual Meeting of the Society for Leukocyte Biology. The meeting was sponsored by the AIRIG and the National Institute on Alcohol Abuse and Alcoholism. The presentations were as follows: (1) Effects of Ethanol on Immune Response to Hepatitis C Virus by Jack R. Wands, (2) Alcohol and Alveolar Macrophage Dysfunction: The Role of Chronic Oxidant Stress by Lou Ann S. Brown, (3) T Cell Responses to Listeria monocytogenes in Mice on a Chronic Ethanol Exposure Protocol by Robert T. Cook, (4) Mechanisms of Acute and Chronic Alcohol Consumption on Severity of Viral Infections by the Liver and Pancreas by Thomas R. Jerrells, (5) Acute and Chronic Effects on Macrophage Ectodomain Shedding: Implications for Lung Host Defenses by Jay K. Kolls, (6) Increased Susceptibility to Pseudomonas Infection of Burn-Injured Mice Given Alcohol Before Injury by Elizabeth J. Kovacs, (7) Regulation of Tumor Necrosis Factor alpha Expression in Macrophages by Chronic Ethanol by Laura E. Nagy, and (8) Hepatitis C Virus Infection and Alcohol Use by Gyongyi Szabo. Meeting coorganizers were Elizabeth J. Kovacs, Lou Ann S. Brown, Thomas R. Jerrells, and Robert T. Cook. PMID:16930226

  12. Management of acute hepatitis B.

    PubMed

    Shiffman, Mitchell L

    2010-02-01

    Acute hepatitis B virus (HBV) is a common cause of acute icteric hepatitis in adults. The vast majority of these patients resolve this acute infection and develop long-lasting immunity. In contrast, the vast majority of patients who develop chronic HBV have minimal symptoms and do not develop jaundice after becoming infected with HBV. These patients will frequently remain undiagnosed for years or decades. Approximately 1% of persons with acute HBV develop acute liver failure. Preventing acute HBV with vaccination is the best treatment. Although universal vaccination is now administered to newborns in many countries, the majority of adults have not been vaccinated and remain at risk. Because the majority of patients with acute HBV resolve this infection spontaneously, treatment with an oral anti-HBV agent is not necessary. However, the use of an oral anti-HBV agent is not unreasonable to use in a patient who is developing acute liver failure from severe acute HBV. PMID:20123442

  13. 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

  14. [Management of severe alcoholic hepatitis].

    PubMed

    Wieser, Verena; Tilg, Herbert

    2014-01-01

    Severe alcoholic hepatitis is still associated with high mortality and presence of liver failure manifested by jaundice, coagulopathy and encephalopathy is a poor prognostic indicator. The management of these patients includes at first hand several supportive measures as treatment of alcohol withdrawal, administration of fluid and vitamins and admission to an intensive care unit in the unstable patient. Glucocorticoids have been since decades the most intensively studied therapy in alcoholic hepatitis and are effective in certain subgroups. Indication for such a therapy is usually defined on a Maddrey Discriminant Function > 32. The Lille score at day 7 is used to decide whether corticosteroid therapy should be stopped or continued for a 1 month course. Nutritional supplementation is also likely to be beneficial. The main progress in better understanding its pathophysiology has come from cytokine studies. Various proinflammatory cytokines such as tumor necrosis factor-alpha (TNF?) or interleukin-1 (IL-1) have been proposed to play a role in this disease. This advancement has recently led to pilot studies investigating anti-TNF drugs such as pentoxifylline, infliximab (anti-TNF antibody) or etanercept in the treatment of this disease. These studies revealed besides for pentoxifylline rather negative results. Despite this fact, targeting of certain cytokines such as IL-1 remains an attractive treatment concept for this devastating disorder in the future. PMID:23842647

  15. [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-? (TNF-?) 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 H2O2 and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-? 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

  16. Peculiar characteristics of portal-hepatic hemodynamics of alcoholic cirrhosis

    PubMed Central

    Bolognesi, Massimo; Verardo, Alberto; Di Pascoli, Marco

    2014-01-01

    Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes that occur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis. PMID:25009370

  17. Hepatitis C Virus and Alcohol

    PubMed Central

    Siu, Larry; Foont, Julie; Wands, Jack R.

    2010-01-01

    This review will focus on the prevalence of hepatitis c virus (HCV) infection in alcoholics with and without liver disease. Evidence will be presented to demonstrate that ethanol and chronic HCV infection synergistically accelerate liver injury. Some of the major postulated mechanisms responsible for disease progression include high rates of apoptosis, lipid peroxidation, and generation of free radicals and reactive oxygen species with reduced antioxidant capacity of the liver. Acquisition and persistence of HCV infection may be due to the adverse effects of ethanol on humoral and cellular immune responses to HCV. Dendritic cells (DC) appear to be one of the major targets for ethanol’s action and DC dysfunction impairs the ability of the host to generate viral specific cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune responses. There is a relationship between increased alcohol intake and decreased response to interferon (IFN) therapy, which may be reversed by abstinence. Clinical studies are needed to optimize treatment responses in alcoholic patients with chronic HCV infection. PMID:19387918

  18. [Acute viral hepatitis during pregnancy].

    PubMed

    Valdés R, Enrique; Sepúlveda M, Alvaro; Candia P, Paula; Lattes A, Karina

    2010-12-01

    Acute hepatitis has a very low incidence disease during pregnancy. However, it may be an important cause of jaundice during gestation which in cases of viral etiology can have a very high morbidity and mortality risk to the mother and the fetus. The purpose of this review is to update the available knowledge regarding viral hepatitis during pregnancy including description of the main etiologies, transmission route, maternal-fetal risk and possible management. PMID:21279287

  19. Serological diagnosis of acute viral hepatitis

    Microsoft Academic Search

    Jay H. Hoofnagle; Antonio Ponzetto; Lars R. Mathiesen; Jeanne G. Waggoner; Z. Buskell Bales; Leonard B. Seeff

    1985-01-01

    Fifty cases of symptomatic acute viral hepatitis presenting at the Washington, D.C., Veterans Administration Medical Center between 1976 and 1977 were tested for serological markers of hepatitis virus infection. The etiology of the acute hepatitis appeared to be hepatitis A virus in 20%, hepatitis B virus in 52%, non-A, non-B agents in 22%, delta hepatitis in 4%, and infectious mononucleosis

  20. [Acute hepatitis in infectious diseases].

    PubMed

    Podymova, S D

    2013-01-01

    Hepatitis A, B, C, D, E, G are the most common causes of acute hepatitis, however, there are many infectious diseases affecting liver and with fever, early diagnostics of which is very important for the clinic of internal diseases. This review presents infections, causing fever and hepatitis, but not necessarily accompanied by jaundice. Leptospirosis, yellow fever have been considered, in which liver damage determines the clinic and the prognosis of the disease. In other cases, such as infectious mononucleosis, cytomegalovirus and herpetic hepatitis, typho-para-typhoid infections, typhoid, pneumonia, some viral diseases, malaria, Legionnaire's disease, hepatitis do not have their independent status and represent one of the important syndromes of a common disease. Modern methods of diagnostics and treatment of these diseases have been described. PMID:24294783

  1. Alcoholic Hepatitis: Steroids vs. Pentoxifylline

    PubMed Central

    Smart, Laura; Gobejishvili, Leila; Crittenden, Neil; Barve, Shirish; McClain, Craig J.

    2013-01-01

    Alcoholic hepatitis (AH) remains a major cause of liver-related morbidity and mortality in the United States and is actually increasing in certain areas of Europe. Thus, there is a pressing need for new therapies/approaches. Major barriers for reducing morbidity, mortality, and costs of care include: lack of translational animal and human studies of new therapies for AH; limited trials of combination therapies in AH targeted at specific disease mechanisms (e.g., gut permeability, cytokines, oxidative stress); limited studies on non-invasive, non-mortality end points; few studies on mechanisms of steroid non-responsiveness; and inadequate prognostic indicators, to name only a few. In spite of these gaps, we have made major advances in understanding mechanisms for AH and appropriate therapies for AH. This article reviews mechanisms and rationale for use of steroids and pentoxifylline in AH and future directions in therapy. PMID:23750115

  2. Alcoholic Hepatitis: Current challenges and future directions

    PubMed Central

    Singal, Ashwani K; Kamath, Patrick S; Gores, Gregory J; Shah, Vijay H

    2013-01-01

    Alcoholic hepatitis is a distinct clinical syndrome amongst people with chronic and active alcohol abuse with a potential for 30–40% mortality at one month amongst those with severe disease. Corticosteroids or pentoxifylline are the current pharmacological treatment options but provide only about 50% survival benefit. These agents are recommended for patients with modified discriminant function (mDF) of ?32 or model for end-stage disease (MELD) score of ?18. The Lille score is used to determine response to steroids. Currently, a minimum of 6 months abstinence from alcohol use is required for patients to receive a liver transplant, a requirement that cannot be met by patients with severe alcoholic hepatitis non-responsive to steroids (Lille score ?0.45). Data are emerging on the benefit of liver transplantation in select patients with first episode of severe alcoholic hepatitis. This review also focuses on recent treatment trials in alcoholic hepatitis including liver transplantation and its associated controversies, as well as possible future targets and pharmacological treatment options for patients with alcoholic hepatitis that are being pursued through upcoming consortium studies. PMID:23811249

  3. Alcoholic hepatitis: current challenges and future directions.

    PubMed

    Singal, Ashwani K; Kamath, Patrick S; Gores, Gregory J; Shah, Vijay H

    2014-04-01

    Alcoholic hepatitis is a distinct clinical syndrome among people with chronic and active alcohol abuse, with a potential for 30%-40% mortality at 1 month among those with severe disease. Corticosteroids or pentoxifylline are the current pharmacologic treatment options, but they provide only about 50% survival benefit. These agents are recommended for patients with modified discriminant function (mDF) ? 32 or Model for End-Stage Liver Disease score ? 18. The Lille score is used to determine response to steroids. Currently, a minimum of 6 months of abstinence from alcohol use is required for patients to receive a liver transplant, a requirement that cannot be met by patients with severe alcoholic hepatitis nonresponsive to steroids (Lille score ? 0.45). Data are emerging on the benefit of liver transplantation in select patients with first episode of severe alcoholic hepatitis. This review also focuses on recent treatment trials in alcoholic hepatitis including liver transplantation and its associated controversies, as well as possible future targets and pharmacologic treatment options for patients with alcoholic hepatitis that are being pursued through upcoming consortium studies. PMID:23811249

  4. Corticosteroids for alcoholic hepatitis—what's next?

    Microsoft Academic Search

    Philippe Mathurin

    2005-01-01

    Alcoholic hepatitis (AH) is observed in approximately 20% of heavy drinkers. The treatment of AH remains controversial and will, in the near future, constitute one of the main challenges to clinicians involved in the manage- ment of severe alcoholic liver disease (1). Individual data from the last three randomized controlled trials (RCT), prospective studies and a recent RCT constantly showed

  5. Hepatitis Bs antibody in alcoholic cirrhosis

    Microsoft Academic Search

    P R Mills; T H Pennington; P Kay; R N MacSween; G Watkinson

    1979-01-01

    Sera from patients with chronic liver disease were tested for antibody against hepatitis B surface antigen by radioimmunoassay. The antibody was found in 25% of patients with alcoholic cirrhosis and in 52% when alcoholic cirrhosis was associated with portal hypertension, these results being significantly higher than in a matched control population. Other forms of chronic liver disease did not differ

  6. Hepatitis Bs antibody in alcoholic cirrhosis.

    PubMed Central

    Mills, P R; Pennington, T H; Kay, P; MacSween, R N; Watkinson, G

    1979-01-01

    Sera from patients with chronic liver disease were tested for antibody against hepatitis B surface antigen by radioimmunoassay. The antibody was found in 25% of patients with alcoholic cirrhosis and in 52% when alcoholic cirrhosis was associated with portal hypertension, these results being significantly higher than in a matched control population. Other forms of chronic liver disease did not differ from the control population. Hepatitis B virus infection might be a factor in determining which alcoholic patients go on to develop chronic liver disease and cirrhosis. PMID:512037

  7. Hepatic encephalopathy in alcoholic cirrhosis.

    PubMed

    Butterworth, Roger F

    2014-01-01

    Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of cirrhosis in alcoholic patients that is characterized clinically by personality changes, sleep abnormalities, and impaired motor coordination, as well as cognitive dysfunction progressing to stupor and coma. Procedures used for diagnosis and grading of HE include neurologic assessment, electroencephalography, psychometric testing, and use of the critical flicker frequency test. Neuropathologically, HE in cirrhosis is principally a disorder of neuroglia characterized by Alzheimer type II astrocytosis and activation of microglia. However, thalamic and cerebellar neuronal pathologies have been noted as well as lesions to globus pallidus and substantia nigra, leading to a condition known as "parkinsonism in cirrhosis." Multiple mechanisms have been proposed to account for the pathogenesis of HE in cirrhosis, including the neurotoxic actions of ammonia and manganese (normally removed via the hepatobiliary route), impaired brain energy metabolism, central proinflammatory mechanisms, and alterations of both excitatory and inhibitory neurotransmission. Treatment of HE in cirrhosis continues to rely on ammonia-lowering strategies such as lactulose, antibiotics, probiotics and l-ornithine l-aspartate with nutritional management consisting of adequate (but not excessive) dietary protein and vitamin B1 supplements. l-DOPA may improve parkinsonian symptoms. Liver transplantation leads to recovery of central nervous system function in the majority of cases. PMID:25307598

  8. Acute hepatitis C virus infection.

    PubMed

    Irving, W L; Salmon, D; Boucher, C; Hoepelman, I M

    2008-05-22

    Around 25% of people infected with hepatitis C virus (HCV) are able to clear the infection spontaneously, while the majority become chronically infected, with a subsequent risk for the individual patient of progressive inflammatory liver disease, cirrhosis, hepatocellular carcinoma and liver-related death (Figure 1). Much is known about the epidemiology, pathogenesis, diagnosis and management of chronic HCV infection. In comparison, knowledge about acute HCV infection is patchy. In this article, we will highlight concerns relating to acute HCV infection and suggest that public health bodies responsible for managing the HCV epidemic should redirect at least some of their resources to dealing with these issues. PMID:18761963

  9. 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

  10. Lamivudine treatment for severe acute HBV hepatitis

    Microsoft Academic Search

    Andrea Lisotti; Francesco Azzaroli; Federica Buonfiglioli; Marco Montagnani; Flavio Alessandrelli; Giuseppe Mazzella

    Treatment for acute hepatitis B is recommended in order to reduce the risk of progression to fulminant hepatitis and the need of OLT. We report our experience on treatment with high dose lamivudine, in patients with severe acute HBV infection. The diagnosis was based on clinical and virological findings and exclusion of other known causes of liver damage. The decision

  11. Severe alcoholic hepatitis-current concepts, diagnosis and treatment options

    PubMed Central

    Kim, Won; Kim, Dong Joon

    2014-01-01

    Alcoholic hepatitis (AH) is an acute hepatic manifestation occurring from heavy alcohol ingestion. Alcoholic steatohepatitis (ASH) is histologically characterized by steatosis, inflammation, and fibrosis in the liver. Despite the wide range of severity at presentation, those with severe ASH (Maddrey’s discriminant function ? 32) typically present with fever, jaundice, and abdominal tenderness. Alcohol abstinence is the cornerstone of therapy for AH and, in the milder forms, is sufficient for clinical recovery. Severe ASH may progress to multi-organ failure including acute kidney injury and infection. Thus, infection and renal failure have a major impact on survival and should be closely monitored in patients with severe ASH. Patients with severe ASH have a reported short-term mortality of up to 40%-50%. Severe ASH at risk of early death should be identified by one of the available prognostic scoring systems before considering specific therapies. Corticosteroids are the mainstay of treatment for severe ASH. When corticosteroids are contraindicated, pentoxifylline may be alternatively used. Responsiveness to steroids should be assessed at day 7 and stopping rules based on Lille score should come into action. Strategically, future studies for patients with severe ASH should focus on suppressing inflammation based on cytokine profiles, balancing hepatocellular death and regeneration, limiting activation of the innate immune response, and maintaining gut mucosal integrity. PMID:25349640

  12. Parvovirus B19 associated acute cholestatic hepatitis.

    PubMed

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

    2014-01-01

    There are few reports in the literature of hepatitis as a manifestation of Parvovirus B19 infection. We describe a case of Parvovirus B19 associated acute cholestatic hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in peripheral blood. Parvovirus B19 infection should be considered in the differential diagnosis of patient presenting with acute hepatitis of unknown etiology. PMID:25669893

  13. Hepatic artery duplex Doppler ultrasound in severe alcoholic hepatitis and correlation with Maddrey’s discriminant function

    PubMed Central

    Abhilash, Haridas; Mukunda, Madhavan; Sunil, Premaletha; Devadas, Krishnadas; Vinayakumar, Katoor Ramakrishnan Nair

    2015-01-01

    Background Alcoholic hepatitis is associated with altered hepatic artery hemodynamics. Maddrey’s discriminant function (MDF) can identify patients with poor prognosis (DF >32). We studied hepatic artery hemodynamic parameters of hepatic artery diameter (HAD), resistive index (RI) and pulsatility index (PI) in severe acute alcoholic hepatitis (SAAH) and for the presence of correlation of parameters with severity factor MDF. Methods A total of 20 consecutive SAAH patients defined as MDF >32 and a group of 20 alcoholic cirrhosis patients without alcoholic hepatitis formed the two study groups. Hepatic artery Doppler parameters HAD, RI, PI were determined after admission in the Gastroenterology Department, Government Medical College, Thiruvananthapuram, India. MDF score of SAAH was calculated at the time of admission to the hospital. Results The mean HAD showed statistically significant increase in SAAH compared with cirrhosis (3.96±0.51 vs. 2.86±0.41, P<0.001). There was statistically significant decrease in mean RI (0.49±0.08 vs. 0.81±0.09, P<0.001) and mean PI (1.67±0.13 vs. 1.80±0.13, P<0.001) in SAAH compared with alcoholic cirrhosis. Statistically significant correlation between MDF and HAD (r=0.63, P<0.003) was found in SAAH. On linear regression, 36% of the variability in MDF could be independently predicted by HAD. Conclusion Hepatic artery parameters of HAD, RI, PI had a significant difference in SAAH compared with alcoholic cirrhosis patients thereby being useful as a diagnostic tool. HAD showed correlation with MDF score assessing the severity of alcoholic hepatitis and may be a useful non-invasive prognostic tool.

  14. Acute Alcohol-Induced Liver Injury

    PubMed Central

    Massey, Veronica L.; Arteel, Gavin E.

    2012-01-01

    Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD) in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation, and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, which also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic. PMID:22701432

  15. Current concepts and controversies in the treatment of alcoholic hepatitis

    PubMed Central

    Rongey, Catherine; Kaplowitz, Neil

    2006-01-01

    The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis. PMID:17109510

  16. Acute alcohol intoxication and female orgasmic response

    Microsoft Academic Search

    Victor J. Malatesta; Robert H. Pollack; Terri D. Crotty; Lelon J. Peacock

    1982-01-01

    This study tested the hypothesis that increasing levels of acute alcohol intoxication are related to systematic changes in female orgasmic experience reflected by physiological, behavioral, and cognitive indices. Using a repeated measures design with monthly experimental sessions, each of 18 university women were sustained at four different blood alcohol concentrations (BAC) in counterbalanced order prior to viewing sexually explicit videotapes

  17. Extracorporeal liver support in severe alcoholic hepatitis

    PubMed Central

    Parés, Albert; Mas, Antoni

    2014-01-01

    The severity of alcoholic hepatitis (AH) which may coexist with cirrhosis varies greatly, from asymptomatic forms which are detected in alcoholic patients without any sign of liver disease, except laboratory abnormalities, to severe forms characterised by deep jaundice, ascites, hepatic encephalopathy and low prothrombin index. In hospitalized patients the mortality could be as high as 75%. The elevated number of therapeutic proposals reported for more than forty years reveals the lack of efficacy of a particular modality. Even in the most favorable trials, the survival is already very poor and in some cases related to the development of renal failure or hepatorenal syndrome. There are some motivating reports concerning albumin dialysis as a support treatment in patients with severe AH, either alone or in combination with other pharmacological therapies. The favorable effects of albumin dialysis in patients with severe AH suggest that the procedure used alone or in combination with other therapies may have a role in this clinical condition. This will be particularly relevant to offer an alternative therapy in these patients, thus being a potential bridge to recovery or to be listed for liver transplantation. PMID:25009371

  18. Role of Fn14 in acute alcoholic steatohepatitis in mice.

    PubMed

    Karaca, Gamze; Xie, Guanhua; Moylan, Cynthia; Swiderska-Syn, Marzena; Guy, Cynthia D; Krüger, Leandi; Machado, Mariana Verdelho; Choi, Steve S; Michelotti, Gregory A; Burkly, Linda C; Diehl, Anna Mae

    2015-02-15

    TNF-like weak inducer of apoptosis (TWEAK) is a growth factor for bipotent liver progenitors that express its receptor, fibroblast growth factor-inducible 14 (Fn14), a TNF receptor superfamily member. Accumulation of Fn14(+) progenitors occurs in severe acute alcoholic steatohepatitis (ASH) and correlates with acute mortality. In patients with severe ASH, inhibition of TNF-? increases acute mortality. The aim of this study was to determine whether deletion of Fn14 improves the outcome of liver injury in alcohol-consuming mice. Wild-type (WT) and Fn14 knockout (KO) mice were fed control high-fat Lieber deCarli diet or high-fat Lieber deCarli diet with 2% alcohol (ETOH) and injected intraperitoneally with CCl? for 2 wk to induce liver injury. Mice were euthanized 3 or 10 days after CCl? treatment. Survival was assessed. Liver tissues were analyzed for cell death, inflammation, proliferation, progenitor accumulation, and fibrosis by quantitative RT-PCR, immunoblot, hydroxyproline content, and quantitative immunohistochemistry. During liver injury, Fn14 expression, apoptosis, inflammation, hepatocyte replication, progenitor and myofibroblast accumulation, and fibrosis increased in WT mice fed either diet. Mice fed either diet expressed similar TWEAK/Fn14 levels, but ETOH-fed mice had higher TNF-? expression. The ETOH-fed group developed more apoptosis, inflammation, fibrosis, and regenerative responses. Fn14 deletion did not reduce hepatic TNF-? expression but improved all injury parameters in mice fed the control diet. In ETOH-fed mice, Fn14 deletion inhibited TNF-? induction and increased acute mortality, despite improvement in liver injury. Fn14 mediates wound-healing responses that are necessary to survive acute liver injury during alcohol exposure. PMID:25524063

  19. Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation

    PubMed Central

    Seth, Devanshi; Duly, Alastair; Kuo, Paul C; McCaughan, Geoffrey W; Haber, Paul S

    2014-01-01

    AIM: To investigate over-expression of Osteopontin (OPN) pathway expression and mechanisms of action in human alcoholic liver disease (ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, ?v?3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell (HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcohol-induced effects on hepatic stellate cell functions and liver fibrogenesis. PMID:25278703

  20. 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

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

    PubMed

    Cacopardo, B; Nunnari, G; Nigro, L

    2009-05-01

    A transient reduction of hepatitis C virus replication during the course of acute hepatitis A virus infection has already been reported in the literature. The present study reports the case study of a subject with chronic hepatitis due to hepatitis C virus who went on to develop an acute hepatitis A. From the early onset of acute disease, hepatitis C virus ribonucleic acid became undetectable. Following recovery from acute hepatitis, alanine amino-transferase levels became persistently normal and liver biopsy revealed a reduction in the Knodell histological activity index score. Hepatitis C virus ribonucleic acid clearance was maintained up to 4 years after the onset of acute hepatitis A. During the course of the acute disease, a sharp increase in interferon gamma levels was detected in serum and in the supernatant of both unstimulated and phytoemagglutinin/lipopolysaccharide-stimulated peripheral blood mononuclear cells. Interferon gamma levels were still high 3 months later. We hypothesize that acute hepatitis A virus superinfection during the course of chronic hepatitis C may lead to hepatitis C virus ribonucleic acid clearance through an immunological mechanism related to interferon gamma production. PMID:18182335

  2. Alverine citrate induced acute hepatitis.

    PubMed

    Arhan, Mehmet; Koklu, Seyfettin; Koksal, Aydln-S; Yolcu, Omer-F; Koruk, Senem; Koruk, Irfan; Kayacetin, Ertugrul

    2004-08-01

    Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent. A 34-year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening. Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment. Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case, several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity. PMID:15259090

  3. Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.

    PubMed

    Zakhari, Samir

    2013-08-01

    Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. PMID:23855291

  4. In vitro and in vivo models of acute alcohol exposure

    PubMed Central

    Dolganiuc, Angela; Szabo, Gyongyi

    2009-01-01

    Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse, and identifies their suitability for biomedical research. PMID:19291816

  5. Comparison of rat pulmonary and hepatic cytosolic alcohol dehydrogenase activities

    Microsoft Academic Search

    Jose E. Manautou; Gary P. Carlson

    1992-01-01

    The liver is the major organ responsible for ethanol oxidation, and alcohol dehydro?genase (ADH) is the main enzyme involved. There is limited evidence suggesting the involvement of the lung in ethanol metabolism. To determine the degree to which pulmonary ADH plays a role in ethanol metabolism, ADH activity was measured spectrophotometrically using hepatic and pulmonary cytosolic fractions prepared by differential

  6. Acute alcohol effects on plasma estradiol levels in women

    Microsoft Academic Search

    Jack H. Mendelson; Scott E. Lukas; Nancy K. Mello; Leslie Amass; James Ellingboe; Alicja Skupny

    1988-01-01

    Acute administration of alcohol (0.695 g\\/kg) to healthy adult women resulted in peak blood alcohol levels between 70 and 75 mg\\/dl within 50–60 min after initiation of drinking. Alcohol induced a significant increase (x=18 pg\\/ml) in plasma estradiol levels (P<0.01). In contrast, after placebo ingestion, plasma estradiol levels did not change significantly. After alcohol intake, plasma estradiol levels reached peak

  7. Hepatitis B antigens in serum and liver of chimpanzees acutely infected with hepatitis B virus.

    PubMed Central

    Berquist, K R; Peterson, J M; Murphy, B L; Ebert, J W; Maynard, J E; Purcell, R H

    1975-01-01

    We report the temporal patterns of various immunohistological and serological parameters of acute self-limited hepatitis B virus infection of two chimpanzees, and we provide evidence that the synthesis of hepatitis B core antigen precedes that of hepatitis B surface antigen. Our data suggest that existence of a biphasic hepatitis B virus infection involving a hematogenous reinfection of the liver and indicate that recruitment of liver cells to produce hepatitis B virus may occur in a pattern consistent with a replicative cycle of about 8 days. PMID:1100525

  8. Acute coronary ischemia during alcohol withdrawal: a case report

    PubMed Central

    2011-01-01

    Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms. Conclusions Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists. PMID:21838872

  9. Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis

    PubMed Central

    Zhou, Peng; Ross, Ruth A.; Pywell, Cameron M.; Liangpunsakul, Suthat; Duffield, Giles E.

    2014-01-01

    To investigate the role of the circadian clock in the development of alcohol-induced fatty liver disease we examined livers of mice chronically alcohol-fed over 4-weeks that resulted in steatosis. Here we show time-of-day specific changes in expression of clock genes and clock-controlled genes, including those associated with lipid and bile acid regulation. Such changes were not observed following a 1-week alcohol treatment with no hepatic lipid accumulation. Real-time bioluminescence reporting of PERIOD2 protein expression suggests that these changes occur independently of the suprachiasmatic nucleus pacemaker. Further, we find profound time-of-day specific changes to the rhythmic synthesis/accumulation of triglycerides, cholesterol and bile acid, and the NAD/NADH ratio, processes that are under clock control. These results highlight not only that the circadian timekeeping system is disturbed in the alcohol-induced hepatic steatosis state, but also that the effects of alcohol upon the clock itself may actually contribute to the development of hepatic steatosis. PMID:24430730

  10. Corticosteroids for severe alcoholic hepatitis: what constitutes response?

    Microsoft Academic Search

    R Hamid; H Lafferty; E Watson; J Winter; A J Morris; A J Stanley; E H Forrest

    2011-01-01

    IntroductionSevere alcoholic hepatitis (AH) is associated with high short term mortality. Although still attracting some controversy, many hospitals will treat severe AH with corticosteroids (CS). Early identification of patients not responding to CS treatment is crucial as continuing treatment may be associated with side-effects and be considered futile. More importantly, identification of CS non-responders (NR) is essential as alternative therapies

  11. Neuropsychological Profile of Acute Alcohol Intoxication during Ascending and Descending Blood Alcohol Concentrations

    Microsoft Academic Search

    Tom A Schweizer; Muriel Vogel-Sprott; James Danckert; Eric A Roy; Amanda Skakum; Carole E Broderick

    2006-01-01

    Numerous studies have investigated the effects of alcohol on motor processes during rising and declining blood alcohol concentrations (BAC), however, relatively little research has examined the alcohol-induced impairment of cognitive performance on the two limbs of the BAC curve. This experiment administered a neuropsychological test battery to assess the degree to which rising and declining BACs during an acute dose

  12. Acute Exacerbation of Chronic Hepatitis B: The Dilemma of Differentiation from Acute Viral Hepatitis B

    PubMed Central

    Puri, Pankaj

    2013-01-01

    Exacerbations of chronic hepatitis B are common in endemic countries. Acute exacerbation of chronic hepatitis B virus (CHB-AE) causing derangement of liver functions may be seen in a flare of HBV in immune clearance phase or as a reactivation of HBV in patients with inactive or resolved HBV infection. While reactivation of HBV is usually seen in HBsAg positive patients, it is being increasingly recognized in patients with apparently resolved HBV infection who do not have HBsAg in serum but have IgG antibody to core antigen (anti-HBc) in the serum, especially so in patients on chemotherapy, immunosuppressive therapy or undergoing hematopoietic stem cell transplantation. In an icteric patient who is HBsAg positive, it may be difficult to differentiate CHB-AE from acute viral hepatitis B (AVH-B). Both may have similar clinical presentation and even IgM anti-HBc, the traditional diagnostic marker of AVH-B, may also appear at the time of exacerbation of CHB. The differentiation between CHB-AE and AVH-B is important not only for prognostication but also because management strategies are different. Most cases of AVH-B will resolve on their own, HBsAg clearance is achieved spontaneously in 90–95% of adults and treatment is rarely indicated except in the few with severe/fulminant disease. In contrast, in CHB-AE, the onset of jaundice may lead to decompensation of liver disease and treatment is warranted. The mechanisms of acute exacerbation and the differentiating features between AVH-B and CHB-AE are reviewed.

  13. Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis

    Microsoft Academic Search

    A Luca; JC Garcia-Pagan; J Bosch; F Feu; J Caballeria; RJ Groszmann; J Rodes

    1997-01-01

    BACKGROUND & AIMS: Increased portal blood flow represents a compensatory mechanism preventing hepatic hypoxia after ethanol consumption. In addition, alcohol increases hepatic vascular resistance. Thus, ethanol consumption, by increasing hepatic vascular resistance and portal flow, may worsen portal hypertension in patients with cirrhosis. The aim of this study was to investigate the effects of ethanol consumption on hepatic hemodynamics in

  14. Diagnosis and management of acute alcohol withdrawal

    Microsoft Academic Search

    Anne M. Holbrook; Renée Crowther; Chiachen Cheng; Derek King

    ALCOHOL ABUSE PRODUCES A CONSIDERABLE BURDEN OF ILLNESS in the Canadian popu- lation. The diagnosis of alcohol dependence and withdrawal can be difficult, particularly in the setting of covert intake or comorbidity. Two validated scales, the CAGE questionnaire to screen for alcohol abuse and dependence and the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale to assess the severity of

  15. 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

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

    SciTech Connect

    Apte, Udayan M. [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); Banerjee, Atrayee [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); McRee, Rachel [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); Wellberg, Elizabeth [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); Ramaiah, Shashi K. [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States)]. 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.

  17. Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association.

    PubMed

    Theochari, Evangelia; Vincent-Smith, Lisa; Ellis, Cathy

    2015-01-01

    Hepatitis E virus infection (HEV) is an emerging pathogen that is under-recognised in developed countries. Preceding infection manifested by acute transaminitis has been associated with neurological manifestations, predominately involving the peripheral nervous system, even in immunocompetent patients. We present a case of a 65-year-old previously fit and well Caucasian man with bilateral neuralgic amyotrophy (NA) and acute transaminitis. Serology testing for immunoglobulin (Ig) M and G established the diagnosis of acute HEV infection. The patient received immunomodulatory treatment with an excellent long-term outcome. The temporal association of the clinical presentation of bilateral NA and acute transaminitis from HEV infection suggested the causal association of HEV to NA. We propose screening for HEV in patients presenting with NA and acute hepatitis. PMID:25739795

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

    PubMed

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

    2015-02-01

    Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization. PMID:25218789

  19. Protracted viremia during acute sporadic hepatitis E virus infection

    Microsoft Academic Search

    Santosh Kumar Nanda; Israrul Haque Ansari; Subrat Kumar Acharya; Shahid Jameel; Subrat Kumar Panda

    1995-01-01

    Background\\/Aims: Hepatitis E virus (HEV) is associated with epidemic and sporadic hepatitis in developing countries. The disease is largely self-limited with no long-term sequelae. The source of HEV for maintenance of the disease in an endemic area is unknown. This study investigated the occurrence and duration of viremia in patients with acute sporadic HEV infection. Methods: In 26 of 37

  20. Hyperglycaemia as an indicator of concurrent acute pancreatitis in fulminant hepatic failure associated with hepatitis B infection

    Microsoft Academic Search

    A Srinivasan; S Venkataraman; S G Hansdak; O C Abraham; D Mathai

    Pancreatitis occurring concurrently with fulminant hepatic failure (FHF) is primarily detected on autopsy and is seldom clinically apparent. We report a fatal case of FHF in a 25-year-old woman which was related to acute hepatitis B infection. In this patient, hyperglycaemia needing insulin infusions led to the detection of acute pancreatitis. FHF complicated by acute pancreatitis has a poor prognosis.

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

    PubMed

    Orenbuch-Harroch, Efrat; Levy, Liran; Ben-Chetrit, Eldad

    2008-12-14

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. In countries with intermediate or high endemicity for HBV, exacerbations of chronic hepatitis B may be the first presentation of HBV infection. Some of these patients may be diagnosed mistakenly as having acute hepatitis B. Accurate diagnosis in these cases is very important for deciding whether to start treatment or not, because acute hepatitis B does not require therapy, while exacerbation of chronic hepatitis may benefit from it. Clinical and routine laboratory findings cannot help distinguishing between these two conditions. Therefore, several assays have been proposed for this purpose during the last few years. The presence of high levels of anti-HBe antibodies, HBsAg and HBV DNA are typical of chronic disease, whereas high titers of IgM anti-HBc, together with their high avidity index, characterize acute HBV infection. Starting from the description of a patient with acute hepatitis B-who recently came to our observation-we critically review the currently available assays that may help distinguishing between the different conditions and lead to the optimal management of each patient. PMID:19084923

  2. Acute onset distal symmetrical vasculitic polyneuropathy associated with acute hepatitis B.

    PubMed

    Mehndiratta, Manmohan; Pandey, Sanjay; Nayak, Rajeev; Saran, Ravindra K

    2013-02-01

    Hepatitis B can have varied extrahepatic manifestations involving the skin, renal, haematological and nervous systems. Neurological manifestations in hepatitis B may take the form of Guillain-Barré syndrome and secondary systemic vasculitis-related mononeuritis multiplex. The clinical course of hepatitis B-related, vasculitis-related neuropathy is usually subacute to chronic and clinical evolution is relatively benign. To our knowledge, acute hepatitis B-associated vasculitis manifesting as acute distal symmetric polyneuropathy has not been reported. We report a 60-year-old man who presented with fever, mild hepatomegaly, skin lesions in the form of non-palpable purpura and acute onset distal symmetric sensorimotor polyneuropathy. Serum transaminase levels were raised and viral serological markers revealed acute hepatitis B. The patient remained anicteric throughout his clinical course. Nerve conduction studies showed severe axonal sensorimotor polyneuropathy and histopathological examination of sural nerve biopsy was suggestive of vasculitic neuropathy. The patient was first given a course of intravenous immunoglobulin with the antiviral drug entecavir. The fever subsided after 1 week of treatment. The patient was started on prednisolone in addition to the entecavir, and showed significant improvement in motor power and marked resolution in paresthesia after 2 weeks of treatment. Thus, acute onset distal symmetric sensorimotor polyneuropathy of vasculitic etiology can be a manifestation of acute hepatitis B. PMID:23164826

  3. Molecular targets in the treatment of alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Lee, Richard WL; Collins, Peter L; McCune, C Anne

    2012-01-01

    Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflammatory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease. PMID:23112542

  4. Global impairment of prospective memory following acute alcohol

    Microsoft Academic Search

    Julie R. Leitz; Celia J. A. Morgan; James A. Bisby; Peter G. Rendell; H. Valerie Curran

    2009-01-01

    Rationale  Whilst the deleterious effects of alcohol on retrospective remembering have been widely documented, no study has yet objectively\\u000a determined alcohol’s effects on prospective memory (PM)—remembering to do something in the future.\\u000a \\u000a \\u000a \\u000a Objectives  With this aim, the present study determined the acute effects of alcohol upon PM using a laboratory measure that simulates\\u000a the PM tasks in everyday life—‘Virtual Week’—both (a) in

  5. Upregulation of Kupffer cell ? 2A-Adrenoceptors and downregulation of MKP-1 mediate hepatic injury in chronic alcohol exposure

    Microsoft Academic Search

    Michael A. Ajakaiye; Asha Jacob; Rongqian Wu; Mian Zhou; Youxin Ji; Weifeng Dong; Zhimin Wang; Xiaoling Qiang; Wayne W. Chaung; Jeffrey Nicastro; Gene F. Coppa; Ping Wang

    2011-01-01

    Alcohol-induced liver disease is associated with unacceptable morbidity and mortality. When activated, Kupffer cells (KCs), the resident macrophages in the liver, release proinflammatory cytokine TNF-?, a key mediator of hepatic damage. Although chronic alcohol causes increase in norepinephrine (NE) release leading to hepatic dysfunction, the mechanism of NE-induced hepatic injury in chronic alcohol exposure has not been elucidated. This study

  6. Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis.

    PubMed

    Akriviadis, E A; Steindel, H; Pinto, P C; Fong, T L; Kanel, G; Reynolds, T B; Gupta, S

    1990-09-01

    Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis. PMID:2199290

  7. Serum Fibronectin Levels in Acute and Chronic Viral Hepatitis Patients

    PubMed Central

    ERTURK, Ayse; CURE, Erkan; OZKURT, Zulal; PARLAK, Emine; CURE, Medine Cumhur

    2014-01-01

    Background: The aim of this study was to investigate the serum fibronectin (FN) levels and liver enzyme activities in patients with acute hepatitis (A, B, C) and chronic viral hepatitis (B, C); determine whether the virus types correlated with disease severity; and assess whether FN could be used as a marker of virus type or disease severity in patients. Methods: A total of 60 subjects were enrolled in the study, including 20 patients with acute hepatitis (A, B, C), 20 with chronic hepatitis (B, C), and 20 healthy controls. Serum fibronectin (FN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and albumin were measured in all patients from blood samples. Results: Serum FN levels were significantly lower in acute (122.9 ?g/mL (SD 43.1), P < 0.001) and chronic hepatitis patients (135.7 ?g/mL (SD 46.0), P < 0 .001) compared to controls 221.4 ?g/mL (SD 32.5). A negative correlation was found between serum FN and AST (r2 = 0.528, P < 0.001), ALT (r2 = 0.425, P < 0.001), and GGT (r2 = 0.339, P < 0.001). Additionally, high serum GGT levels (? = –0.375, P = 0.010), and low serum albumin levels (? = –0.305, P = 0.008) were associated with low serum FN levels. Conclusion: Serum FN levels were lower in both acute and chronic hepatitis patients, and an inverse relationship between serum FN and serum AST, ALT, and GGT levels was found. A decrease in serum FN levels may indicate hepatitis severity as AST and ALT represent hepatocyte damage. PMID:24639609

  8. Cryoglobulinemia in acute type-A hepatitis.

    PubMed Central

    Shalit, M; Wollner, S; Levo, Y

    1982-01-01

    Serum cryoglobulins were detected in 18 of 19 patients with type-A, and six of eight with type-B hepatitis. The predominant immunoglobulin in the cryoprecipitates was polyclonal IgM. Patients with type-A hepatitis had a significantly higher mean serum level of cryoglobulins when compared to those with type-B (106.9 vs. 20.5 micrograms/ml). IgM anti-hepatitis-A virus activity was detected in all cryoprecipitates obtained from hepatitis-A patients. Cryoglobulinemia in these patients was transient, associated with disease activity and accompanied by a marked increase in serum level of IgM. These findings are compatible with a recent hypothesis, which predicts the appearance of cryoglobulins under circumstances of enhanced stimulation of B cells in the presence of defective clearance of desialylated glycoproteins by their specific liver receptors. PMID:7083634

  9. Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model

    PubMed Central

    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 ?-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-?1 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-?1/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

  10. The Association of Viral Hepatitis and Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.; Olsen, Harvey; Swanson, Virginia; Rinderknecht, Heinrich

    1972-01-01

    The histological features of 24 pancreases obtained from patients who died of causes other than hepatitis, pancreatitis or pancreatic tumors, included a variable degree of autolysis, rare foci of inflammatory reaction but no hemorrhagic fat necrosis or destruction of elastic tissue in vessel walls (elastolysis). Assays of elastase in extracts of these pancreases showed no free enzyme, but varying amounts of proelastase. A review of autopsy findings in 33 patients with fatal liver necrosis attributed to halothane anesthesia, demonstrated changes of acute pancreatitis only in two. On the other hand, a review of 16 cases of fulminant viral hepatitis revealed changes characteristic of acute pancreatitis in seven – interstitial edema, hemorrhagic fat necrosis, inflammatory reaction and frequently elastolysis in vessel walls. Determination of elastase in extracts of one pancreas showed the bulk of the enzyme in free form. Furthermore, assays of urinary amylase in 44 patients with viral hepatitis showed increased levels of this enzyme (2583 ± 398 mean value ± standard error, Somogyi units per 100 ml in 13, or 29.5 percent). The evidence suggests that acute pancreatitis may at times complicate viral hepatitis. Although direct proof of viral pancreatic involvement is not feasible at present, a rational hypothesis is advanced which underlines similar mechanisms of tissue involvement in both liver and pancreas that may be brought about by the hepatitis viruses. PMID:5070694

  11. Insulin and glucagon therapy of acute hepatic failure

    Microsoft Academic Search

    K. Fujiwara; I. Ogata; Y. Sato; T. Tomiya; Y. Ohta; Y. Oka; S. Nagoshi; S. Yamada; N. Masaki; K. Takatsuki; S. Hayashi; H. Oka

    1991-01-01

    When insulin and glucagon are administered to rats with severe liver injury, survival is enhanced with an attenuation of the liver injury compared to that of untreated controls. In rats with acute liver injury both hormones produce a rapid normalization of hepatic protein content following initiation of DNA synthesis. When rats receive both hormones after partial hepatectomy, the first burst

  12. Antiviral therapy in acute viral hepatitis B: why and when.

    PubMed

    Morelli, Giuseppe; Perrella, Alessandro; Sbreglia, Costanza; Bellopede, Pasquale; Riccio, Vincenzo; Perrella, Oreste

    2009-01-01

    Acute viral hepatitis B is cleared in more than 95% of patients, while the remainder ones may develop either chronic HBV infection or, rarely, fulminant hepatitis.Therefore there are elderly patients with severe acute HBV hepatitis caractherized by high serum bilirubin levels >15 mmole/dl, international normalized ratio (INR) with value more than 1.6; these patients are caractherized by a severe outcome of HBV infection.As known, outcome of infection and the pathogenesis of liver diseases are determined by viral and host factors, such as T reg lymphocytes.T regs may be associated with a negative immune response such as an inhibition of gamma- IFN secretion.The impact of viral load on antiviral T cell responses may play a critical role in these patients, influencing disease persistence and immune response.Antiviral drugs could be useful in these patients determing a possible down -regulation of T regs. PMID:19149879

  13. Antiviral therapy in acute viral hepatitis B: why and when

    PubMed Central

    Morelli, Giuseppe; Perrella, Alessandro; Sbreglia, Costanza; Bellopede, Pasquale; Riccio, Vincenzo; Perrella, Oreste

    2009-01-01

    Acute viral hepatitis B is cleared in more than 95% of patients, while the remainder ones may develop either chronic HBV infection or, rarely, fulminant hepatitis. Therefore there are elderly patients with severe acute HBV hepatitis caractherized by high serum bilirubin levels >15 mmole/dl, international normalized ratio (INR) with value more than 1.6; these patients are caractherized by a severe outcome of HBV infection. As known, outcome of infection and the pathogenesis of liver diseases are determined by viral and host factors, such as T reg lymphocytes. T regs may be associated with a negative immune response such as an inhibition of gamma- IFN secretion. The impact of viral load on antiviral T cell responses may play a critical role in thaese patients, influencing disease persistence and immune response. Antiviral drugs could be useful in these patients determing a possible down -regulation of T regs. PMID:19149879

  14. Hepatitis e as a cause of acute jaundice syndrome in northern Uganda, 2010-2012.

    PubMed

    Gerbi, Gemechu B; Williams, Roxanne; Bakamutumaho, Barnabas; Liu, Stephen; Downing, Robert; Drobeniuc, Jan; Kamili, Saleem; Xu, Fujie; Holmberg, Scott D; Teshale, Eyasu H

    2015-02-01

    Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7-24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda. PMID:25448237

  15. 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

  16. Acute Renal Failure Complicating Viral Hepatitis in the Absence of Severe Hepatic Insufficiency

    Microsoft Academic Search

    Jesús Montoliu; Antonio Coca; Francisco Martinez-Orozco; Alejandro Darnell; Ramón Subías; Luis Revert

    1985-01-01

    Four patients (2 were HBsAg positive) with acute icteric viral hepatitis (VH) developed acute renal failure (ARF) in the course of their illness and in the absence of other complications. Their peak serum creatinine values (4.7–10, mean 7 mg\\/dl) were reached either before or simultaneously with their maximum serum aminotransferase values (1,390–2730, mean 2,032 mU\\/ml). Apart from VH no other

  17. Hepatitis B and A virus antibodies in alcoholic steatosis and cirrhosis.

    PubMed Central

    Gluud, C; Aldershvile, J; Henriksen, J; Kryger, P; Mathiesen, L

    1982-01-01

    Sera from 74 alcoholics with cirrhosis and 63 alcoholics with steatosis were tested for antibody to hepatitis B surface antigen, to hepatitis B core antigen, and to hepatitis A virus by radioimmunoassay or enzyme-linked immunosorbent assay. No significant difference between the two groups of alcoholics could be found concerning the prevalence of these antibodies. The total group of patients had antibody to hepatitis B surface antigen or hepatitis B core antigen, or both, significantly (p less than 0.001) more often (26%) than sex- and age-matched controls (4%). No significant difference was found between patients and controls concerning the prevalence of antibody to hepatitis A virus (46% v 40%). In patients with cirrhosis, no correlation between wedged hepatic vein pressure or wedged-to-free hepatic vein pressure and any of the viral antibodies could be established. The present results suggest that hepatitis B virus does not play a major role in the progression of alcoholic liver disease, but longitudinal studies are needed to solve this problem. The reason for the increased prevalence of antibodies to hepatitis B virus in these patients is unknown. PMID:6284803

  18. SHORT REPORT Open Access Acute risk for hepatitis E virus infection among

    E-print Network

    Paris-Sud XI, Université de

    SHORT REPORT Open Access Acute risk for hepatitis E virus infection among HIV-1-positive pregnant: Hepatitis E virus (HEV), an enterically transmitted pathogen, is highly endemic in several African countries. Pregnant women are at particularly high risk for acute or severe hepatitis E. In Gabon, a central African

  19. Differentiating acute hepatitis B from the first episode of symptomatic exacerbation of chronic hepatitis B.

    PubMed

    Kumar, Manoj; Jain, Sanjay; Sharma, Barjesh Chander; Sarin, Shiv Kumar

    2006-03-01

    In countries with intermediate or high endemicity for chronic hepatitis B virus (HBV) infection, exacerbations of chronic hepatitis B (CHB) are common. We studied the clinical, biochemical, and virologic characteristics of patients first presenting clinically with features of acute icteric hepatitis B, to identify features that might differentiate between acute viral hepatitis B (AVHB) from first episode of exacerbation of chronic hepatitis (ECHB). We retrospectively analyzed 79 patients (mean age 35.4 +/- 14 years; M:F = 60:19) who first presented clinically as AVHB, within 4 weeks of onset of symptoms. Patients who on follow-up cleared HBsAg and/or did not develop any clinical, radiologic, or histologic evidence of chronic liver disease (CLD) were categorized as AVHB (group 1). Patients who had persistence of HBsAg and developed clinical, biochemical, radiologic, or histologic evidence of chronic liver disease were categorized as ECHB (group 2). Forty-nine patients were in group 1 and 30 in group 2. The 2 groups were comparable with respect to prodrome, onset of jaundice, serum bilirubin, ALT, prothrombin time prolongation, serum albumin, and A/G ratio. Among group 1 patients, 78% had IgM anti-HBc positive in titers > 1:1000; in group 2, there were negative or positive in titers < 1:1000 in 70% patients (P < .001). Forty-seven of 49 (95.9%) patients in group 1 had HBV-DNA levels < 0.5 pg/mL, whereas 26 of 30 (86.73%) patients in group 2 had levels > 0.5 pg/mL (P < or = .001). Quantitative HBV DNA and IgM anti-HBc titers at initial presentation can differentiate patients with a true episode of acute hepatitis B from patients with first episode of symptomatic exacerbation of chronic hepatitis B. Clinical and biochemical features do not help in differentiating the two. PMID:16614972

  20. Hepatitis B and C markers among alcoholics in Israel: high incidence of HCV infection.

    PubMed

    Srugo, I; Shinar, E; Bar-Shany, S; Amos, L

    1998-06-01

    Patients with alcoholic liver disease have an increased prevalence of viral hepatitis. However, the role of demographic characteristics has not been adequately delineated. Therefore, we examined and compared the seroprevalences of hepatitis B and C in Israeli alcoholic patients to that of blood donors control group by their country of birth and origin. Hepatitis B surface antigen, hepatitis B core antibody and hepatitis C virus antibody testing (second generation ELISA) and a confirmatory recombinant immunoblot assay was performed on 496 alcoholic attending an alcoholic abstinence program and compared to 193,806 randomly non-alcoholic blood donors on the basis of their country of birth. Three hundred twenty-eight alcoholic patients (66%) were immigrants and Israeli born Jews and 168 (34%) were Israeli Arabs. Of the 496 alcoholic patients, 24 (4.8%) were HBsAg positive, 38 (7.6%) were anti HCV positive, and 2 (North African Jews) were positive for both markers. HBsAg was detected in 13 (3.9%) immigrant and Israeli Jews and 11 (6.5%) Israeli Arabs, significantly higher than in the adjusted non alcoholic blood donors (p < 0.01). Anti-HCV was detected in 33 (10%) immigrants and Israeli Jews and 5 (2.9%) Israeli Arabs, significantly higher than in the control group (p < 0.005). In the subgroup alcoholic Jews there was no significant difference in hepatitis B seropositivity among alcoholic that were native Israeli, Eastern Europe and former USSR, and Western Europe and American immigrants comparing to the control group. In contrast, anti-HCV recombinant immunoblot assay seropositivity in alcoholic Jews from all subgroups was significantly greater than in non alcoholic blood donors (p < 0.001). Odds analysis of all ethnic groups revealed that alcoholism requiring detoxification have a significant risk factor for hepatitis C more than hepatitis B (p < 0.001). The increased seroprevalence of hepatitis C among Israeli alcoholic patients, regardless their country of birth and origin, suggest that alcoholism is likely to have a predisposing factor for HCV infection. PMID:9690749

  1. Role of Hepatic Resident and Infiltrating Macrophages in Liver Repair after Acute Injury

    PubMed Central

    You, Qiang; Holt, Michael; Yin, Hao; Li, Guiying; Hu, Cheng-Jun; Ju, Cynthia

    2013-01-01

    Treatment of liver disease, caused by hepatotoxins, viral infections, alcohol ingestion, or autoimmune conditions, remains challenging and costly. The liver has a powerful capacity to repair and regenerate, thus a thorough understanding of this tightly orchestrated process will undoubtedly improve clinical means of restoring liver function after injury. Using a murine model of acute liver injury caused by overdose of acetaminophen (APAP), our studies demonstrated that the combined absence of liver resident macrophages (Kupffer cells, KCs), and infiltrating macrophages (IMs) resulted in a marked delay in liver repair, even though the initiation and extent of peak liver injury was not impacted. This delay was not due to impaired hepatocyte proliferation but rather prolonged vascular leakage, which is caused by APAP-induced liver sinusoidal endothelial cell (LSEC) injury. We also found that KCs and IMs express an array of angiogenic factors and induce LSEC proliferation and migration. Our mechanistic studies suggest that hypoxia-inducible factor (HIF) may be involved in regulating the angiogenic effect of hepatic macrophages (Macs), as we found that APAP challenge resulted in hypoxia and stabilization of HIF in the liver and hepatic Macs. Together, these data indicate an important role for hepatic Macs in liver blood vessel repair, thereby contributing to tissue recovery from acute injury. PMID:23876342

  2. Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.

    PubMed

    You, Qiang; Holt, Michael; Yin, Hao; Li, Guiying; Hu, Cheng-Jun; Ju, Cynthia

    2013-09-15

    Treatment of liver disease, caused by hepatotoxins, viral infections, alcohol ingestion, or autoimmune conditions, remains challenging and costly. The liver has a powerful capacity to repair and regenerate, thus a thorough understanding of this tightly orchestrated process will undoubtedly improve clinical means of restoring liver function after injury. Using a murine model of acute liver injury caused by overdose of acetaminophen (APAP), our studies demonstrated that the combined absence of liver resident macrophages (Kupffer cells, KCs), and infiltrating macrophages (IMs) resulted in a marked delay in liver repair, even though the initiation and extent of peak liver injury was not impacted. This delay was not due to impaired hepatocyte proliferation but rather prolonged vascular leakage, which is caused by APAP-induced liver sinusoidal endothelial cell (LSEC) injury. We also found that KCs and IMs express an array of angiogenic factors and induce LSEC proliferation and migration. Our mechanistic studies suggest that hypoxia-inducible factor (HIF) may be involved in regulating the angiogenic effect of hepatic macrophages (Macs), as we found that APAP challenge resulted in hypoxia and stabilization of HIF in the liver and hepatic Macs. Together, these data indicate an important role for hepatic Macs in liver blood vessel repair, thereby contributing to tissue recovery from acute injury. PMID:23876342

  3. Pathogenesis of alcoholic hepatitis: Role of inflammatory signaling and oxidative stress

    PubMed Central

    Jampana, Sarat C; Khan, Rashid

    2011-01-01

    Inflammatory signaling and oxidative stress are two major components in the pathogenesis of alcoholic hepatitis. Alcohol consumption results in translocation of gut bacteria into the portal system along with lipopolysaccharides that interact with toll-like receptors and results in the production of inflammatory and immunogenic mediators such as tumor necrosis factor-alpha (TNF-?) and interferons. Chronic consumption of alcohol causes priming of this process in which there is enhanced production of cytokines, interferon, interleukins, and TNF-?. Oxidative stress, genetic predisposition, and the unfolded protein response are other contributory mechanisms. Novel therapies aimed at these pathways may prevent, decrease, or delay the complications of alcoholic hepatitis. PMID:21731903

  4. 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-? (TNF-?), interleukin-1? (IL-1?) 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

  5. 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-? (TNF-?), interleukin-1? (IL-1?) 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

  6. 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

  7. Influence of chronic alcohol consumption on hepatic heme and porphyrin metabolism.

    PubMed

    Teschke, R; Gorys-Könemann, C; Daldrup, T; Goerz, G

    1987-04-01

    To study the effect of prolonged alcohol consumption on hepatic heme and porphyrin metabolism, female Wistar rats were fed for 60 days a nutritionally adequate liquid diet containing 36% of total calories as ethanol, whereas the control diet was isocaloric and contained no alcohol. Compared to pair-fed controls, the administration of the alcohol diet resulted in an increased hepatic activity of delta-aminolevulinic acid synthase by 223% (112.3 +/- 19.6 nmoles/hr/100 g b.wt. vs. 362.8 +/- 42.5; P less than 0.01), an enhanced urinary excretion of delta-aminolevulinic acid by 101% (64.8 +/- 11.8 nmoles/day vs. 130.8 +/- 22.4; P less than 0.05), and an augmented urinary output of total porphyrins by 142% (1.2 +/- 0.2 nmoles/day vs. 2.9 +/- 0.5; P less than 0.05). Concomitantly, the hepatic content of cytochrome P-450 was significantly enhanced and that of hepatic catalase activity marginally increased, whereas the hepatic iron content remained unaltered. In summary, the feeding of rats with a liquid alcohol diet for 60 days results in changes of hepatic heme and porphyrin metabolism which are associated and may be causally related with an induction of hepatic hemoproteins and subsequent derepression of hepatic delta-aminolevulinic acid synthase, whereas hepatic iron appears to play no pathogenic role. PMID:3566807

  8. Taurine Protects Immature Cerebellar Granullar Neurons against Acute Alcohol Administration

    Microsoft Academic Search

    Andrey G. Taranukhin; Elena Y. Taranukhina; Irina M. Djatchkova; Pirjo Saransaari; Markku Pelto-Huikko; Simo S. Oja

    Acute ethanol administration causes extensive apoptosis throughout the nervous system. We studied the protective effect of\\u000a taurine on alcohol-induced apoptosis in the cerebellum of developing mice. Taurine rescued a part of immature neurons by markedly\\u000a reducing caspase-3 immunoreactivity and the number of TUNEL-positive cells in most cerebellar lobules.

  9. 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 ?-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751

  10. Early mortality of alcoholic hepatitis: A review of data from placebo-controlled clinical trials

    PubMed Central

    Yu, Chao-Hui; Xu, Cheng-Fu; Ye, Hua; Li, Lan; Li, You-Ming

    2010-01-01

    AIM: To investigate the early mortality of placebo-treated alcoholic hepatitis patients. METHODS: Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. RESULTS: A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infection were the three main causes of death, accounting for 55.47%, 21.17% and 7.30% of all deaths, respectively. One-month mortality data about 324 placebo-treated alcoholic hepatitis patients in 10 trials were reported with a pooled mortality rate of 20.37%. The one-month mortality rate of patients with moderate to severe alcoholic hepatitis tended to be higher than that of general patients (22.69% vs 10.93%, P < 0.05), whereas no significant difference was observed between the patients from North America or Europe (22.43% vs 18.45%, P > 0.05), neither any difference was found between the studies published before and after 1990 (18.18% vs 21.88%, P > 0.05). CONCLUSION: Alcoholic hepatitis is a severe liver disease with a high mortality rate, and hepatic failure, gastrointestinal bleeding and infection are the three main causes of death. PMID:20480532

  11. Clostridium septicum infection of hepatic metastases following alcohol injection: a case report.

    PubMed

    Saleh, Neam; Sohail, Muhammad R; Hashmey, Rayhan H; Al Kaabi, Mohammed

    2009-01-01

    Clostridium septicum infections are generally associated with gastrointestinal or hematologic malignancies. We report the first case of hepatic metastases infection with Clostridium septicum that followed alcohol injection of liver lesion. Clinicians should consider this possibility in patients with underlying malignancy who present with hepatic abscess, as prompt surgical drainage and empiric antibiotics may be life saving. PMID:20072687

  12. 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

  13. Hepatitis E and Acute-on-Chronic Liver Failure

    PubMed Central

    Kumar, Ashish; Saraswat, Vivek A.

    2013-01-01

    Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials.

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

    PubMed

    Ye?ilyurt, Murat; K?l?ç, 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

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

    PubMed Central

    Kimbi, Gerald C; Kramvis, Anna; Kew, Michael C

    2005-01-01

    AIM: To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation. METHODS: DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced. RESULTS: HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right virus/host junction was situated at nucleotide 1 774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged. The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time. CONCLUSION: Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis. PMID:16425409

  16. Molecular Mechanisms of Alcohol-Induced Hepatic Fibrosis

    Microsoft Academic Search

    Sören V. Siegmund; Steven Dooley; David A. Brenner

    2005-01-01

    Alcohol abuse is a major cause of liver fibrosis and cirrhosis in developed countries. Before alcoholic liver fibrosis becomes evident, the liver undergoes several stages of alcoholic liver disease including steatosis and steatohepatitis. Although the main mechanisms of fibrogenesis are independent of the etiology of liver injury, alcoholic liver fibrosis is distinctively characterized by a pronounced inflammatory response due to

  17. Increased Risk of Acute Hepatitis B among Adults with Diagnosed Diabetes Mellitus

    PubMed Central

    Reilly, Meredith L.; Schillie, Sarah F.; Smith, Emily; Poissant, Tasha; Vonderwahl, Candace W.; Gerard, Kristin; Baumgartner, Jennifer; Mercedes, Lynne; Sweet, Kristin; Muleta, Daniel; Zaccaro, Daniel J.; Klevens, R. Monina; Murphy, Trudy V.

    2012-01-01

    Introduction The risk of acute hepatitis B among adults with diabetes mellitus is unknown. We investigated the association between diagnosed diabetes and acute hepatitis B. Methods Confirmed acute hepatitis B cases were reported in 2009–2010 to eight Emerging Infections Program (EIP) sites; diagnosed diabetes status was determined. Behavioral Risk Factor Surveillance System respondents residing in EIP sites comprised the comparison group. Odds ratios (ORs) comparing acute hepatitis B among adults with diagnosed diabetes versus without diagnosed diabetes were determined by multivariate logistic regression, adjusting for age, sex, and race/ethnicity, and stratified by the presence or absence of risk behaviors for hepatitis B virus (HBV) infection. Results During 2009–2010, EIP sites reported 865 eligible acute hepatitis B cases among persons aged ?23 years; 95 (11.0%) had diagnosed diabetes. Comparison group diabetes prevalence was 9.1%. Among adults without hepatitis B risk behaviors and with reported diabetes status, the OR for acute hepatitis B comparing adults with and without diabetes was 1.9 (95% confidence interval [CI] = 1.4, 2.6); ORs for adults ages 23–59 and ?60 years were 2.1 (95% CI = 1.6, 2.8) and 1.5 (95% = CI 0.9, 2.5), respectively. Conclusions Diabetes was independently associated with an increased risk for acute hepatitis B among adults without HBV risk behaviors. PMID:22920812

  18. Association of parvovirus B19 infection with acute icteric hepatitis in adults.

    PubMed

    Sun, Li; Zhang, Jiu-Cong; Jia, Zhan-Sheng

    2011-07-01

    Infection by human parvovirus B19 is widespread and can be associated with a wide range of different pathologies and clinical manifestations. However, parvovirus B19 infection associated with hepatitis or hepatic dysfunction in adults is rarely reported. We describe two cases of acute icteric hepatitis associated with parvovirus B19 infection in adults. PMID:21284565

  19. 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

  20. 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

  1. ASMASE IS REQUIRED FOR CHRONIC ALCOHOL INDUCED HEPATIC ENDOPLASMIC RETICULUM STRESS AND MITOCHONDRIAL CHOLESTEROL LOADING

    PubMed Central

    Fernandez, Anna; Matias, Núria; Fucho, Raquel; Ribas, Vicente; Von Montfort, Claudia; Nuño, Natalia; Baulies, Anna; Martinez, Laura; Tarrats, Núria; Mari, Montserrat; Colell, Anna; Morales, Albert; Dubuquoy, Laurent; Mathurin, Philippe; Bataller, Ramón; Caballeria, Joan; Elena, Montserrat; Balsinde, Jesus; Kaplowitz, Neil; Garcia-Ruiz, Carmen; Fernandez-Checa, Jose C.

    2013-01-01

    Background & aims The pathogenesis of alcohol-induced liver disease (ALD) is poorly understood. Here, we examined the role of acid sphingomyelinase (ASMase) in alcohol induced hepatic endoplasmic reticulum (ER) stress, a key mechanism of ALD Methods We examined ER stress, lipogenesis, hyperhomocysteinemia, mitochondrial cholesterol (mChol) trafficking and susceptibility to LPS and concanavalin-A in ASMase?/? mice fed alcohol. Results Alcohol feeding increased SREBP-1c, DGAT-2 and FAS mRNA in ASMase+/+ but not in ASMase?/? mice. Compared to ASMase+/+ mice, ASMase?/? mice exhibited decreased expression of ER stress markers induced by alcohol, but the level of tunicamycin-mediated upregulation of ER stress markers and steatosis was similar in both types of mice. The increase in homocysteine levels induced by alcohol feeding was comparable in both ASMase+/+ mice and ASMase?/? mice. Exogenous ASMase, but not neutral SMase, induced ER stress by perturbing ER Ca2+ homeostasis. Moreover, alcohol-induced mChol loading and StARD1 overexpression were blunted in ASMase?/? mice. Tunicamycin upregulated StARD1 expression and this outcome was abrogated by tauroursodeoxycholic acid. Alcohol-induced liver injury and sensitization to LPS and concanavalin-A were prevented in ASMase?/? mice. These effects were reproduced in alcohol-fed TNFR1/R2?/? mice. Moreover, ASMase does not impair hepatic regeneration following partial hepatectomy. Of relevance, liver samples from patients with alcoholic hepatitis exhibited increased expression of ASMase, StARD1 and ER stress markers. Conclusion Our data indicate that ASMase is critical for alcohol-induced ER stress, and provide a rationale for further clinical investigation in ALD. PMID:23707365

  2. 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...

  3. Hepatic Myelopathy in a Patient with Decompensated Alcoholic Cirrhosis and Portal Colopathy

    PubMed Central

    Premkumar, Madhumita; Bagchi, Avishek; Kapoor, Neha; Gupta, Ankit; Maurya, Gaurav; Vatsya, Shubham; Kapahtia, Siddharth; Kar, Premashish

    2012-01-01

    Cirrhotic or hepatic myelopathy is a rare neurological complication of chronic liver disease usually seen in adults and presents as a progressive pure motor spastic paraparesis which is usually associated with overt liver failure and a surgical or spontaneous systemic portocaval shunt. We describe the development of progressive spastic paraparesis, in a patient with alcoholic cirrhosis with portal hypertension and portal colopathy who presented with the first episode of hepatic encephalopathy. The patient had not undergone any shunt procedure. PMID:25374709

  4. Alcohol and Hepatocellular Carcinoma: The Effect of Lifetime Intake and Hepatitis Virus Infections in Men and Women

    Microsoft Academic Search

    F. Donato; A. Tagger; U. Gelatti; G. Parrinello; P. Boffetta; A. Albertini; A. Decarli; P. Trevisi; M. L. Ribero; C. Martelli; S. Porru; G. Nardi

    2002-01-01

    The authors investigated the dose-effect relation between alcohol drinking and hepatocellular carcinoma (HCC) in men and women separately, also considering hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380 men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected by hepatic diseases as controls; all were hospitalized in Brescia, northern Italy, in

  5. Gene expression profile analysis of rat cerebellum under acute alcohol intoxication.

    PubMed

    Zhang, Yu; Wei, Guangkuan; Wang, Yuehong; Jing, Ling; Zhao, Qingjie

    2015-02-25

    Acute alcohol intoxication, a common disease causing damage to the central nervous system (CNS) has been primarily studied on the aspects of alcohol addiction and chronic alcohol exposure. The understanding of gene expression change in the CNS during acute alcohol intoxication is still lacking. We established a model for acute alcohol intoxication in SD rats by oral gavage. A rat cDNA microarray was used to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). A total of 251 differentially expressed genes were identified in response to acute alcohol intoxication, in which 208 of them were up-regulated and 43 were down-regulated. Gene ontology (GO) term enrichment analysis and pathway analysis revealed that the genes involved in the biological processes of immune response and endothelial integrity are among the most severely affected in response to acute alcohol intoxication. We discovered five transcription factors whose consensus binding motifs are overrepresented in the promoter region of differentially expressed genes. Additionally, we identified 20 highly connected hub genes by co-expression analysis, and validated the differential expression of these genes by real-time quantitative PCR. By determining novel biological pathways and transcription factors that have functional implication to acute alcohol intoxication, our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of acute alcoholism. PMID:25527120

  6. Human and Experimental Evidence Supporting a Role for Osteopontin in Alcoholic Hepatitis

    PubMed Central

    Morales-Ibanez, Oriol; Domínguez, Marlene; Ki, Sung H.; Marcos, Miguel; Chaves, Javier F.; Nguyen-Khac, Eric; Houchi, Hakim; Affò, Silvia; Sancho-Bru, Pau; Altamirano, José; Michelena, Javier; García-Pagán, Juan Carlos; Abraldes, Juan G.; Arroyo, Vicente; Caballería, Juan; Laso, Francisco-Javier; Gao, Bin; Bataller, Ramón

    2013-01-01

    We identified in the transcriptome analysis of patients with alcoholic hepatitis (AH) osteopontin (OPN) as one of the most up-regulated genes. Here, we used a translational approach to investigate its pathogenic role. OPN hepatic gene expression was quantified in patients with AH and other liver diseases. OPN protein expression and processing were assessed by immmunohistochemistry, Western blotting and ELISA. OPN gene polymorphisms were evaluated in patients with alcoholic liver disease. The role of OPN was evaluated in OPN?/? mice with alcohol-induced liver injury. OPN biological actions were studied in human hepatic stellate cells and in precision-cut liver slices. Hepatic expression and serum levels of OPN were markedly increased in AH compared to normal livers and other types of chronic liver diseases and correlated with short-term survival. Serum levels of OPN also correlated with hepatic expression and disease severity. OPN was mainly expressed in areas with inflammation and fibrosis. Two proteases that process OPN (thrombin and MMP-7) and cleaved-OPN were increased in livers with AH. Patients with AH had a tendency of a lower frequency of the CC genotype of the +1239C SNP of the OPN gene compared to patients with alcohol abuse without liver disease. Importantly, OPN?/? mice were protected against alcohol-induced liver injury and showed decreased expression of inflammatory cytokines. Finally, OPN was induced by LPS and stimulated inflammatory actions in hepatic stellate cells. Conclusion Human and experimental data suggest a role for OPN in the pathogenesis of AH. Further studies should evaluate OPN as a potential therapeutic target. PMID:23729174

  7. Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences

    Microsoft Academic Search

    Blythe D. Shepard; David J. Fernandez; Pamela L. Tuma

    2010-01-01

    Alcoholic liver disease is a major biomedical health concern in the United States. Despite considerable research efforts aimed\\u000a at understanding the progression of the disease, the specific mechanisms leading to alcohol-induced damage remain elusive.\\u000a Numerous proteins are known to have alcohol-induced alterations in their dynamics. Defining these defects in protein trafficking\\u000a is an active area of research. In general, two

  8. HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

    PubMed

    Mamun-Al-Mahtab; Rahman, Salimur; Khan, Mobin; Karim, Fazal

    2009-02-01

    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 micromol/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. Pathogenesis of hepatic steatosis: The link between hypercortisolism and non-alcoholic fatty liver disease

    PubMed Central

    Tarantino, Giovanni; Finelli, Carmine

    2013-01-01

    Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing’s syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing’s syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing’s syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing’s syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease. PMID:24187449

  10. The association of syphilis with cirrhosis: the role of alcohol and serum hepatitis

    PubMed Central

    Sadikali, F.

    1975-01-01

    The role of syphilis and alcohol was investigated in a prospective study of patients with cirrhosis of liver in Uganda, and results were correlated with the histological type of cirrhosis, and serological tests for hepatitis B antigen (HB Ag). Eighteen out of eighty (22·5%) patients with histologically-proven cirrhosis had positive serology for syphilis (VDRL and TPI). A high incidence of alcoholism (80%) and syphilis (60%) was found in patients with micronodular cirrhosis who were all negative for HB Ag. By contrast, HB Ag was detected in 37% of patients with macronodular cirrhosis who had a much smaller incidence of syphilis and alcoholism. Although chronic infection with hepatitis B virus related to HB Ag appears to be an important factor in the pathogenesis of cirrhosis in at least 30% of cases, infection acquired during past treatment for syphilis is not an important cause of the association of syphilis with cirrhosis in this population. Subdivision of patients with cirrhosis into those with and those without a history of severe alcohol abuse showed that the difference between the incidence of syphilis in the two groups is significant statistically. However, evidence of syphilis in association with non-alcoholic as well as alcoholic cirrhosis in this and other previously reported series suggests that the association between the two diseases cannot be entirely explained through the common factor of alcoholism, and other factors may also be responsible. PMID:1114150

  11. High precision liquid chromatography analysis of dopaminergic and serotoninergic responses to acute alcohol exposure in zebrafish

    Microsoft Academic Search

    Diptendu Chatterjee; Robert Gerlai

    2009-01-01

    Zebrafish is gaining popularity in behavioral neuroscience in general and in alcohol research in particular. Alcohol is known to affect numerous molecular mechanisms depending on dose and administration regimen. Prominent among these mechanisms are several neurotransmitter systems. Here we analyze the responses of the dopaminergic and serotoninergic neurotransmitter systems of zebrafish to acute alcohol treatment (1h long exposure of adult

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

    SciTech Connect

    Lieber, Charles S. [Section of Liver Disease and Nutrition, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)], E-mail: liebercs@aol.com; Leo, Maria Anna [Section of Liver Disease and Nutrition, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Wang, Xiaolei [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); DeCarli, Leonore M. [Section of Liver Disease and Nutrition, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States)

    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.

  13. 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

  14. 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.

  15. Transient receptor potential vanilloid 1 gene deficiency ameliorates hepatic injury in a mouse model of chronic binge alcohol-induced alcoholic liver disease.

    PubMed

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

    2015-01-01

    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 Ca(2+) 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-?, 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

  16. [Kwashiorkor in an adult with alcoholic hepatic cirrhosis].

    PubMed

    Cotter, J; Camilo, M E; Correia, J P

    1989-01-01

    Multifactorial malnutrition is common in alcoholic cirrhosis. We report a case dominated by Kwashiorkor due to malabsorption related to infestation with Giardia Lamblia. Malnutrition deserves a complete investigation in order to detect treatable causes. PMID:2624157

  17. 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

  18. CD14 promoter polymorphism in Chinese alcoholic patients with cirrhosis of liver and acute pancreatitis

    Microsoft Academic Search

    You-Chen Chao; Heng-Cheng Chu; Wei-Kuo Chang; Hsin-Hung Huang; Tsai-Yuan Hsieh

    2005-01-01

    Abstract Abstract Abstract Abstract AIM: To investigate the relationship between genetic polymorphism of the CD14 promoter and the occurrence of alcoholic cirrhosis and alcoholic pancreatitis, and to challenge the conclusion made earlier that the patients with acute alcoholic pancreatitis and patients with alcoholic cirrhosis of liver are two different subpopulations. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)

  19. 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

  20. Acute Kidney Dysfunction in Patients with Chronic Hepatitis C Virus Infection: Analysis of Viral and Non-viral Factors

    PubMed Central

    Satapathy, Sanjaya K.; Lingisetty, Chandra S.; Williams, Susan E.

    2014-01-01

    Background Multiple studies have shown a relationship between chronic hepatitis C infection and chronic kidney disease. The prevalence, severity, underlying etiologies and predictors of acute kidney dysfunction (AKD) events in patients with hepatitis C has not been studied. Methods We investigated viral and non-viral factors in the development renal dysfunction in 468 HCV patients retrospectively over a period of observation ranging from 3 months to 6 yrs. Results A total of 124 AKD events occurred in 63 patients. On regression analysis; gender, race, alcohol abuse, HIV (Human immune deficiency virus) status, body mass index, baseline viral load (HCV–PCR), and genotype did not predict an event of AKD. Decompensated liver disease, history of IVDU, diabetes mellitus and baseline creatinine were independent predictors of AKD. Conclusion Development of AKD in patient with hepatitis C virus infection is independent of the genotype and viral load at baseline and is mostly predisposed by known prevalent factors in patients with hepatitis C such as diabetes, hypertension and intravenous drug use. Decompensated liver disease is the single most viral-related factor that predisposes for AKD. PMID:25755529

  1. Albumin dialysis improves hepatic encephalopathy and decreases circulating phenolic aromatic amino acids in patients with alcoholic hepatitis and severe liver failure

    Microsoft Academic Search

    Albert Parés; Ramón Deulofeu; Laura Cisneros; Angels Escorsell; Joan Manuel Salmerón; Joan Caballería; Antoni Mas

    2009-01-01

    Introduction  The aim of this study was to assess the effects of albumin dialysis on hepatic encephalopathy and circulating levels of amino\\u000a acids in severe alcoholic hepatitis.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The study was carried out in nine patients with severe alcoholic hepatitis and four with primary biliary cirrhosis treated\\u000a with the molecular adsorbent recirculating system. Besides standard liver function tests, circulating levels of ammonia,

  2. Acute and chronic aquatic toxicity structure–activity relationships for alcohol ethoxylates

    Microsoft Academic Search

    D. D Morrall; S. E Belanger; J. C Dunphy

    2003-01-01

    Acute and chronic toxicity tests using the cladoceran Daphnia magna were conducted on several alcohol ethoxylate surfactants. Exposure and homologue distributions were confirmed using specific analytical methods. These data were used to test currently available acute structure–activity relationships (SARs) and to develop a new chronic SAR to extrapolate test data to effluent or receiving water mixtures. Existing acute SARs adequately

  3. Experimental Alcohol-Induced Hepatic Necrosis: Suppression by Propylthiouracil

    Microsoft Academic Search

    Y. Israel; H. Kalant; H. Orrego; J. M. Khanna; L. Videla; J. M. Phillips

    1975-01-01

    We have previously reported that a hypermetabolic state, resembling that produced by thyroid hormones, exists in the livers of animals treated chronically with ethanol. We propose that this alteration produces a relative hypoxia in the centrilobular zone of the liver which, if severe enough, leads to cellular death and to the production of hepatitis. Rats consuming ethanol for 30 days,

  4. Epidemiological and virological characteristics of symptomatic acute hepatitis E in Greater Cairo, Egypt.

    PubMed

    Delarocque-Astagneau, E; Abravanel, F; Moshen, A; Le Fouler, L; Gad, R R; El-Daly, M; Ibrahim, E M; El-Aidy, S; Lashin, T; El-Hoseiny, M; Izopet, J; Mohamed, M K; Fontanet, A; Abdel Hamid, M

    2012-10-01

    The aim of the study was to describe the characteristics of acute hepatitis E in Greater Cairo. Patients with acute hepatitis E were identified through a surveillance of acute hepatitis using the following definition: recent (<3 weeks) onset of fever or jaundice, alanine aminotransferase at least three times the upper limit of normal (uln), negative markers for other causes of viral hepatitis and detectable hepatitis E virus (HEV) RNA. Comparison of the liver tests between acute hepatitis E and hepatitis A virus (HAV), case-control analysis (four sex-matched and age-matched (±1 year) HAV controls per case) to explore risk factors and phylogenetic analyses were performed. Of the 17 acute HEV patients identified between 2002 and 2007, 14 were male. Median age was 16 years (interquartile range 13-22). Compared with HAV (n = 68 sex-matched and ±1 year age-matched), HEV patients had higher bilirubin (mean (SD) 10.9 (5.7) uln versus 7.5 (4.4) uln, p 0.05) and aspartate aminotransferase levels (38.6 (27.1) uln versus 18.3 (18.1) uln, p 0.02). Co-infection (hepatitis C virus RNA or hepatitis B surface (HBs) -antigen positive/IgM anti-hepatitis B core (HBc) anitgen negative) was diagnosed in four patients. In univariate matched analysis (17 cases, 68 matched controls), HEV cases were more likely to live in a rural area than HAV controls (matched OR 7.9; 95% CI 2.0-30.4). Of the 16 isolates confirmed as genotype 1, 15 belonged to the same cluster with 94-98.5% identity in the open-reading frame 2 region. Our findings documented the sporadic nature of HEV in Greater Cairo, characterized a large number of Egyptian HEV genotype 1 strains and identified living in a rural area as a potential risk factor for infection. PMID:22264267

  5. Risk factors and immune response to hepatitis E viral infection among acute hepatitis patients in Assiut, Egypt.

    PubMed

    Eldin, Salwa S Seif; Seddik, Ismail; Daef, Enas A; Shata, M T; Raafat, Marwa; Abdel Baky, Laila; Nafeh, M A

    2010-01-01

    Hepatitis E virus (HEV) infection is a common cause of acute viral hepatitis (AVH) in Egypt. We aimed to identify risk factors of HEV among acute hepatitis cases, measure HEV specific immune response to differentiate between symptomatic and asymptomatic infections. The study included symptomatic acute hepatitis (AH) patients (n = 235) and asymptomatic contacts (n = 200) to HEV cases. They completed a lifestyle questionnaire, screened for common hepatotropic viruses. Blood and serum samples were collected from patients and contacts after onset of disease and follow-up samples collected until convalescence. PBMC were separated and tested for specific HEV T-cell response by INF-gamma ELISPOT assay. Serum samples were tested for IgM and IgG anti-hepatitis E virus by ELISA. IgM antibodies to HAV were detected in 19 patients (8.1%), 37 (15.7%) with HBV, 10 (4.3%) with HCV. HEV infection was identified in 42 (16%) patients with AVH. Of the 200 contacts, 14 (7%) had serological evidence of recent HEV asymptomatic infection, showed stronger CMI responses than HEV infected subjects (2540 +/- 28 and 182 +/- 389 ISCs/106 cells, respectively; P < 0.05). In conclusion, HEV is a major cause of AVH in Egypt. Asymptomatic HEV patients are likely to have stronger immune responses including CMI responses, than symptomatic cases. PMID:22053611

  6. Risk Factors and Immune Response to Hepatitis E viral Infection among Acute Hepatitis Patients in Assiut, Egypt

    PubMed Central

    Seif Eldin, Salwa S.; Seddik, Ismail; Daef, Enas A.; Shata, M.T.; Raafat, Marwa; Baky, Laila Abdel; Nafeh, MA

    2011-01-01

    Hepatitis E virus (HEV) infection is a common cause of acute viral hepatitis (AVH) in Egypt. We aimed to identify risk factors of HEV among acute hepatitis cases, measure HEV specific immune response to differentiate between symptomatic and asymptomatic infections. The study included symptomatic acute hepatitis (AH) patients (n=235) and asymptomatic contacts (n=200) to HEV cases. They completed a lifestyle questionnaire, screened for common hepatotropic viruses. Blood and serum samples were collected from patients and contacts after onset of disease and follow-up samples collected until convalescence. PBMC were separated and tested for specific HEV T-cell response by INF-ELISPOT assay. Serum samples were tested for IgM and IgG anti-hepatitis E virus by ELISA. IgM antibodies to HAV were detected in 19 patients (8.1%), 37 (15.7%) with HBV, 10 (4.3%) with HCV. HEV infection was identified in 42 (16%) patients with AVH. Of the 200 contacts, 14 (7%) had serological evidence of recent HEV asymptomatic infection, showed stronger CMI responses than HEV infected subjects (2540 ± 28 and 182 ± 389 ISCs/106 cells, respectively; P <0.05). In conclusion, HEV is a major cause of AVH in Egypt. Asymptomatic HEV patients are likely to have stronger immune responses including CMI responses, than symptomatic cases. PMID:22053611

  7. Alcoholic liver disease

    PubMed Central

    Walsh, K.; Alexander, G.

    2000-01-01

    Alcohol is a major cause of liver cirrhosis in the Western world and accounts for the majority of cases of liver cirrhosis seen in district general hospitals in the UK. The three most widely recognised forms of alcoholic liver disease are alcoholic fatty liver (steatosis), acute alcoholic hepatitis, and alcoholic cirrhosis. The exact pathogenesis of alcoholic liver injury is still not clear but immune mediated and free radical hepatic injury are thought to be important. There is increasing interest in genetic factors predisposing to hepatic injury in susceptible individuals. Diagnosis is based on accurate history, raised serum markers such as ?-glutamyltransferase, mean corpuscular volume, and IgA and liver histology when obtainable. Abstinence is the most important aspect of treatment. Newer drugs such as acamprosate and naltrexone are used to reduce alcohol craving. Vitamin supplements and nutrition are vital while corticosteroids have a role in acute alcoholic hepatitis where there is no evidence of gastrointestinal haemorrhage or sepsis. Liver transplantation has excellent results in abstinent patients with end stage liver disease but there are concerns about recidivism after transplant.???Keywords: cirrhosis; liver disease; alcohol PMID:10775280

  8. Acute hepatitis caused by alverine associated with anti-lamin A and C autoantibodies.

    PubMed

    Malka, D; Pham, B N; Courvalin, J C; Corbic, M; Pessayre, D; Erlinger, S

    1997-08-01

    We report the case of a 67-year-old woman in whom onset and regression of acute hepatitis were closely related to the time of administration and withdrawal of the smooth muscle relaxant alverine. Antinuclear antibodies were positive, and their titer followed the course of hepatitis. They presented a smooth rim-like nuclear immunofluorescence staining pattern. Immunoblot assay showed that they were directed against lamin A and lamin C. This suggests that alverine should be added to the list of drugs known to produce acute hepatitis, and that drug-induced liver injury is a possible cause of antinuclear antibodies specific for lamin A and lamin C. PMID:9288616

  9. Acute Alcohol Effects on Neuronal and Attentional Processing: Striatal Reward System and Inhibitory Sensory Interactions under Acute Ethanol Challenge

    Microsoft Academic Search

    Mathias Schreckenberger; Rainer Amberg; Armin Scheurich; Matthias Lochmann; Wolfgang Tichy; André Klega; Thomas Siessmeier; Gerhard Gründer; Hans-Georg Buchholz; Christian Landvogt; Jan Stauss; Klaus Mann; Peter Bartenstein; Reinhard Urban

    2004-01-01

    The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental

  10. Corticosteroids and pentoxifylline for the treatment of alcoholic hepatitis: Current status

    PubMed Central

    Singal, Ashwani K; Walia, Ishmeet; Singal, Anjna; Soloway, Roger D

    2011-01-01

    The treatment of choice for patients with severe alcoholic hepatitis (AH) is use of corticosteroids. Many randomized well designed studies have been reported from all over the world on the use of corticosteroids in the treatment of AH. However, the data on the efficacy of corticosteroids in these patients have been conflicting. Initial meta-analyses also failed to show beneficial effects of corticosteroids. Based on individual data meta-analysis showing clear benefit of corticosteroids amongst patients with severe AH (modified discriminant function of 32 or more), led American College of Gastroenterology to recommend use of corticosteroids as the first line treatment option amongst patients with severe AH. However, corticosteroids are relatively contraindicated amongst patients with severe AH and coexistent sepsis, gastrointestinal bleeding, and acute pancreatitis. These patients may be candidates for second line treatment with pentoxifylline. Further, specific treatment of AH with corticosteroids far from satisfactory with as many as 40%-50% of patients failing to respond to steroids, thus classified as non-responsive to steroids. The management of these patients is a continuing challenge for physicians. Better treatment modalities need to be developed for this group of patients in order to improve the outcome of patients with severe AH. This article describes at length the available trials on use of corticosteroids and pentoxifylline with their current status. Route of administration, dosage, adverse effects, and mechanisms of action of these two drugs are also discussed. Finally, an algorithm with clinical approach to management of patients who present with clinical syndrome of AH is described. PMID:21954408

  11. Effects of acute ethanol exposure on hepatic metallothionein, zinc and glutathione in male and female rats

    SciTech Connect

    Harris, J.; Harrell, B. (Univ. of Kansas Medical Center, Kansas City (United States))

    1991-03-15

    The purpose of this study was to determine the simultaneous responses of hepatic metallothionein (MT), zinc (Zn) and glutathione (GSH) in male and female rats to an acute ethanol dose. In male rats, hepatic MT has been shown to be induced by an acute ethanol dose. The Sprague-Dawley rats were fed the Lieber-DeCarli control diet for a five day period and then divided into 6 groups: baseline females and males, ethanol-treated females and males, pair-fed females and males. At t=0, baseline rats were killed, ethanol-treated rats were given ethanol by intragastric tube, and pair-fed rats were given ethanol by intragastric tube, and pair-fed rats were given an isocaloric sucrose solution by intragastric tube. At t=24 h, the ethanol-treated and pair-fed rats were killed. Livers were assayed for MT. Zn and GSH. Concentrations of blood ethanol (BEC) were significantly greater for male than female rats. A two way ANOVA with the independent variables being time and sex was performed to analyze differences for hepatic MT, Zn and GSH. For rats dosed with ethanol and killed 24 h later compared with rats at baseline, hepatic MT was significantly greater and hepatic Zn and GSH were not significantly different. Hepatic MT, Zn and GSH were not significantly different by sex. A significant correlation existed between hepatic Zn/g and MT/g. In conclusion, 24 h after an acute dose of ethanol, female as well as male rats responded with the induction of hepatic MT; and enough cysteine was available for the induction of hepatic MT and the maintenance of hepatic GSH levels. The measurement of Zn bound to hepatic MT rather than total hepatic Zn would be desirable to discern if changes in Zn distribution occur.

  12. Clinical features and outcome of acute hepatitis B in pregnancy

    PubMed Central

    2014-01-01

    Background The impact of pregnancy on the clinical course of acute hepatitis B (AHB) is still largely unclear, mainly because most studies have not included matched controls. This study was conducted to investigate the clinical features and outcome of AHB in pregnancy using matched controls. Methods Consecutive AHB inpatients who were admitted to Jinan Infectious Disease Hospital, Jinan, between January 2006 and December 2010 were evaluated and followed. Demographic data, clinical manifestations, and results of laboratory tests were compared between pregnant patients and age and sex matched non-pregnant patients at admission, discharge, and final follow-up. Results A total of 618 AHB inpatients were identified during the study period. 22 pregnant patients and 87 age and sex matched non-pregnant patients were enrolled in this study. Prodromal fever was less common (0% vs. 20.7%, P?=?0.02), serum alanine aminotransferase levels were significantly lower, and HBsAg?>?250 IU/mL rate and serum bilirubin levels were significantly higher in pregnant patients than in non-pregnant patients. After a mean (range) of 7(5.2-8.3) months follow-up, 18.2% pregnant patients and 4.6% non-pregnant patients were still HBsAg positive (P?=?0.03). For pregnant patients, the relative risk (95% confidence interval) of HBsAg positive at the end of follow-up was 4.6 (1.1-20.2). The median (95% confidence interval) days of HBsAg seroclearance form disease onset in pregnant and non-pregnant patients were 145.0 (110.5-179.5) and 80.0 (62.6-97.4), respectively. Conclusions The HBsAg loss and seroconversion were delayed and lower in pregnant patients. Pregnancy might be a possible risk of chronicity following acute HBV infection. PMID:24993389

  13. [Clinical, virological and epidemiological aspects of acute B hepatitis in the Catania area (Italy)].

    PubMed

    Scalia, Guido; Russo, Raffaela; Palermo, Ilenia; Gussio, Maria; Bellissimo, Francesco; Fatuzzo, Filippo; Montineri, Arturo; Patamia, Ildebrando; Costanzo, Maria; Zappala, Daniela; Russo, Rosario; Cacopardo, Bruno

    2010-09-01

    Starting from January 1997 we prospectively evaluated all cases of acute hepatitis B admitted to two of the main Infectious Diseases Units in Catania (eastern Sicily). The survey was extended throughout a 10-year period up to December 2007. Between 1997 and 1999 we observed 21 cases of acute hepatitis B; between 2000 and 2002 18 cases; between 2003 and 2005 22 cases and, finally, 37 cases were reported in the period 2006-2007. We found an increase in acute hepatitis B cases among people aged 26 to 44 years (from 38% in 1997-99 to 70% in 2006-07). A progressive decrease in intravenous drug abuse as a risk factor for acute hepatitis B was also observed (from 61% to 14%) together with a parallel increase in cases due to sexual transmission (from 19% to 56%) and outpatient cosmetic surgical procedures. Mean time to serum HBsAg negativization was longer in the last period (2006-07), with 6 cases out of 37 showing HBsAg persistence beyond 12 months from the clinical onset. Furthermore, in 2006-07 there were 12 cases (42%) of acute hepatitis due to HBV genotypes A and F. In our area, a progressive drop of hepatitis B cases due to intravenous drug abuse occurred, whereas heterosexual and iatrogenic cases increased. Cases due to HBV non-D genotypes may well be related to migration from endemic areas towards Sicily. PMID:20956872

  14. 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

  15. Acute and chronic alcohol administration: effects on performance of zebrafish in a latent learning task.

    PubMed

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

    2015-04-01

    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, 30min 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% (v/v%) alcohol. Subsequently, fish were immersed for 1h in one of the following solutions: 0.00 (freshwater), 0.50% or 1.00% alcohol, the acute challenge. 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 traveled, 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

  16. Predictors of Alcohol Use Among Rural Drug Users After.Disclosure of Hepatitis C Virus Status

    PubMed Central

    Stephens, Dustin B.; Havens, Jennifer R.

    2013-01-01

    Objective: Alcohol consumption dramatically increases the risk of liver damage among those with hepatitis C virus (HCV) infection, yet the impact of HCV status disclosure and standard informational counseling on alcohol use among rural drug users remains poorly understood. Method: In this prospective study, 503 rural Appalachian drug users were recruited using respondent-driven sampling. Participants were tested for HCV antibodies, and data on sociodemographic characteristics, lifetime and past-30-day drug and alcohol use, and psychiatric disorders were collected by interviewer-administered questionnaires. A total of 470 participants returned after 6 months for follow-up; however,4 of those had no history of alcohol use, thus leaving a final sample size of 466. Multivariate negative binomial regression was used to determine the effect of disclosure of HCV status and posttest counseling on alcohol consumption at follow-up. Results: Despite an overall decrease in drinking frequency in the cohort, those who were HCV-positive were drinking at a frequency similar to their HCV-negative counterparts at follow-up, despite posttest counseling informing them of the risks of alcohol use with an HCV diagnosis (adjusted incidence rate ratio = 1.07, 95% CI [0.72, 1.61]). Significant predictors of increased days of alcohol use after 6 months included baseline alcohol use, baseline marijuana use, and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for antisocial personality disorder. Those using OxyContin at baseline had significantly fewer days of alcohol use at follow-up. Conclusions: HCV status disclosure and standard informational counseling alone do not curtail drinking among HCV-positive drug users in the rural setting. Targeted interventions with regard to alcohol use are warranted in order to mitigate the damage of the HCV epidemic. PMID:23490567

  17. Hepatitis C core antigen testing: a reliable, quick, and potentially cost-effective alternative to hepatitis C polymerase chain reaction in diagnosing acute hepatitis C virus infection.

    PubMed

    Cresswell, Fiona V; Fisher, Martin; Hughes, Daniel J; Shaw, Simon G; Homer, Gary; Hassan-Ibrahim, Mohammed O

    2015-01-15

    Hepatitis C virus (HCV) is increasingly common among human immunodeficiency virus (HIV)-infected men who have sex with men. We evaluated the efficacy of HCV core antigen in diagnosing acute HCV in an HIV-infected cohort. Compared with HCV polymerase chain reaction, core antigen proved sensitive (100%) and specific (97.9%). As a quick, simple, and cost-effective test, it has considerable utility in screening for acute HCV. PMID:25301216

  18. Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis

    PubMed Central

    Jalan, R; Turjanski, N; Taylor-Robinson, S; Koepp, M; Richardson, M; Wilson, J; Bell, J; Brooks, D

    2000-01-01

    BACKGROUND/AIMS—To measure cerebral benzodiazepine receptor binding using 11C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy.?METHODS—Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of 11C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances.?RESULTS—The mean volume of distribution of 11C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls.?CONCLUSIONS—The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.???Keywords: benzodiazepine receptors; chronic hepatic encephalopathy; 11C-flumazenil; in vivo proton magnetic resonance spectroscopy; positron emission tomography PMID:10716686

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

    SciTech Connect

    Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.ed [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States); Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    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 ALCOHOL EXPOSURE IMPAIRS FRACTURE HEALING AND DEREGULATES ?-CATENIN SIGNALING IN THE FRACTURE CALLUS

    PubMed Central

    Lauing, Kristen L.; Roper, Philip M.; Nauer, Rachel K.; Callaci, John J.

    2012-01-01

    Background Alcohol abuse is a risk factor for bone damage and fracture-related complications. Through precise ?-catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol-induced impaired fracture healing. Methods Male C57Bl/6 or TCF-transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid-shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post-fracture for analysis of biomechanical strength, callus tissue composition, and Wnt/?-catenin signaling. Results Acute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post-fracture. Histology revealed an alcohol-related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3-fold increase in total ?-catenin protein at day 6 and a significant decrease of 53% and 56% at days 9 and 14 respectively. LacZ staining in ?-galactosidase-expressing TCF-transgenic mice revealed spatial and quantitative differences in Wnt-specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post-fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total ?-catenin protein levels observed at these time points. Conclusions Acute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein ?-catenin, and disruption of normal Wnt-mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone, and may partially explain why impaired fracture healing is observed in alcohol-abusing individuals. PMID:22691115

  1. Upregulation of Kupffer cell ?2A–adrenoceptors and downregulation of MKP-1 mediate hepatic injury in chronic alcohol exposure

    PubMed Central

    Ajakaiye, Michael; Jacob, Asha; Wu, Rongqian; Zhou, Mian; Ji, Youxin; Dong, Weifeng; Wang, Zhimin; Qiang, Xiaoling; Chaung, Wayne W.; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2011-01-01

    Alcohol-induced liver disease is associated with unacceptable morbidity and mortality. When activated, Kupffer cells (KCs), the resident macrophages in the liver, release proinflammatory cytokine TNF-?, a key mediator of hepatic damage. Although chronic alcohol causes increase in norepinephrine (NE) release leading to hepatic dysfunction, the mechanism of NE-induced hepatic injury in chronic alcohol exposure has not been elucidated. This study was conducted to determine whether chronic alcohol exposure increases NE and upregulates KC ?2A-adrenoceptors (?2A-AR) to cause TNF-? release. We also examined the role of mitogen activated protein kinase (MAPK) phosphatase-1 (MKP-1) in this process. Male adult rats were fed the Lieber-DeCarli liquid diet containing alcohol as 36% of total calories. The animals were sacrificed after 6 weeks and blood and liver samples were harvested for further analysis. KCs from healthy male rats were cultured with alcohol for 7 days, and cells then harvested for RNA and protein analyses. Chronic alcohol exposure resulted in hepatic damage. Alcohol caused a 276% increase in circulating NE and 86% increase in TNF-? in the liver. There was a 75% and 62% decrease in MKP-1 mRNA and protein levels in the liver, respectively. In-vitro experiments revealed 121% and 98% increase in TNF-? and ?2A-AR mRNA levels with alcohol exposure, respectively, and a 32% decrease in MKP-1 mRNA compared to controls. In summary, chronic alcohol exposure elevates NE and upregulates KC ?2A-AR to release TNF-?. Alcohol induced downregulation of MKP-1 leads to further release of TNF-? and hepatic injury. PMID:21575605

  2. 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

  3. Trends of acute hepatitis B notification rates in eastern China from 2005 to 2013.

    PubMed

    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

  4. Chronic alcohol-induced hepatic insulin resistance and ER stress ameliorated by PPAR-? agonist treatment

    PubMed Central

    Ramirez, Teresa; Tong, Ming; Cy Chen, William; Nguyen, Quynh-Giao; Wands, Jack R.; de la Monte, Suzanne M.

    2014-01-01

    Background Chronic alcoholic liver disease is associated with hepatic insulin resistance, dysregulated lipid metabolism with increased toxic lipid (ceramide) accumulation, lipid peroxidation, and oxidative and endoplasmic reticulum (ER) stress. Peroxisome-proliferator activated receptor (PPAR) agonists are insulin sensitizers that can restore hepatic insulin responsiveness in both alcohol and non-alcohol-related steatohepatitis. Herein, we demonstrate that treatment with a PPAR-? agonist enhances insulin signaling and reduces the severities of ER stress and ceramide accumulation in an experimental model of ethanol-induced steatohepatitis. Methods Adult male Long Evans rats were pair fed with isocaloric liquid diets containing 0% or 37% ethanol (caloric) for 8 weeks. After 3 weeks on the diets, rats were treated with vehicle or PPAR-? agonist twice weekly by i.p. injection. Results Ethanol-fed rats developed steatohepatitis with inhibition of signaling through the insulin and insulin-like growth factor-1 receptors, and Akt activated pathways. Despite continued ethanol exposure, PPAR-? agonist co-treatments increased Akt activation, reduced multiple molecular indices of ER stress and steatohepatitis. Conclusions These results suggest that PPAR-? agonist rescue of chronic alcoholic liver disease is mediated by enhancement of insulin signaling through Akt/metabolic pathways that reduce lipotoxicity and ER stress. PMID:22988930

  5. Effect of acute alcohol ingestion on plasma pyridoxal 5'-phosphate13

    Microsoft Academic Search

    Telfair H. Parker; Jay P. Marshall II; Roderick K Roberts; Sherry Wang; Eugene R. Sch; Grant R. Wilkinson; Steven Schenker

    This study assesses the effect of acute alcohol intake on net plasma pyridoxal 5'- phosphate (PLP) accumulation from pyridoxine and on PLP elimination from plasma. Unanesthe- tized dogs were given oral alcohol (1 or 3 g\\/kg as a 25% solution in normal saline), isocaloric glucose, or were fasted. Two hours later pyridoxine (1 mg\\/kg iv) was given and serial plasma

  6. 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

  7. Effects of acute alcohol intoxication on cerebral blood flow measured with PET

    Microsoft Academic Search

    Nora D. Volkow; Nizar Mullani; Lance Gould; Stephen S. Adler; Robert W. Guynn; John E. Oveiall; Stephen Dewey

    1988-01-01

    Regional distribution ofcerebral blood flow was assessed in a group of I3 normal social drinkers under baseline conditions and after acute alcohol intoxica- tion. Blood flow measurements were done using 150-labeled water and positron emission tomography (PET). Each subject underwent two control sessions under baseline conditions and two sessions after alcohol. Seven of the subjects were given 0.5 g\\/ kg

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

    PubMed

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

    2015-01-01

    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

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

    Microsoft Academic Search

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

    2011-01-01

    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,

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

    Microsoft Academic Search

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

    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,

  11. Altered benzodiazepine receptor sensitivity in alcoholism: A study with fMRI and acute lorazepam challenge

    Microsoft Academic Search

    Ralf G. M. Schlösser; Thomas Gesierich; Gerd Wagner; Matthias Bolz; Gerhard Gründer; Thomas F. Dielentheis; Claudius Scherb; Peter Stoeter

    2007-01-01

    Previous studies suggested altered sensitivity of the GABA\\/benzodiazepine receptor system in alcoholic patients. Expanding on these findings, the present functional magnetic resonance imaging (fMRI) study aimed to assess whether a differential modulation of cognitive brain activation by an acute GABAergic drug challenge could be detected in patients with alcoholism. Eight detoxified male patients meeting DSM-IV criteria for alcohol dependence and

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

    Microsoft Academic Search

    Bianca Watson; KATHERINE M. CONIGRAVE; Cate Wallace; JOHN B. WHITFIELD; Friedrich Wurst; PAUL S. HABER

    2007-01-01

    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

  13. Attenuation of microglial and IL-1 signaling protects mice from acute alcohol-induced sedation and/or motor impairment.

    PubMed

    Wu, Yue; Lousberg, Erin L; Moldenhauer, Lachlan M; Hayball, John D; Robertson, Sarah A; Coller, Janet K; Watkins, Linda R; Somogyi, Andrew A; Hutchinson, Mark R

    2011-06-01

    Alcohol-induced proinflammatory central immune signaling has been implicated in the chronic neurotoxic actions of alcohol, although little work has examined if these non-neuronal actions contribute to the acute behavioral responses elicited by alcohol administration. The present study examined if acute alcohol-induced sedation (loss of righting reflex, sleep time test) and motor impairment (rotarod test) were influenced by acute alcohol-induced microglial-dependent central immune signaling. Inhibition of acute alcohol-induced central immune signaling, through the reduction of proinflammatory microglial activation with minocycline, or by blocking interleukin-1 (IL-1) receptor signaling using IL-1 receptor antagonist (IL-1ra), reduced acute alcohol-induced sedation in mice. Mice treated with IL-1ra recovered faster from acute alcohol-induced motor impairment than control animals. However, minocycline led to greater motor impairment induced by alcohol, implicating different mechanisms in alcohol-induced sedation and motor impairment. At a cellular level, I?B? protein levels in mixed hippocampal cells responded rapidly to alcohol in a time-dependent manner, and both minocycline and IL-1ra attenuated the elevated levels of I?B? protein by alcohol. Collectively these data suggest that alcohol is capable of rapid modification of proinflammatory immune signaling in the brain and this contributes significantly to the pharmacology of alcohol. PMID:21276848

  14. 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

  15. 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

  16. EFFECTS OF LIGHT AND DARK BEERS ON HEPATIC CYTOCHROME P450 EXPRESSION IN MALE RATS RECEIVING ALCOHOLIC BEVERAGES AS PART OF TOTAL ENTERAL NUTRITION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Alcoholic beverages contain many congeners in addition to ethanol. Therefore, consumption of alcoholic beverages may have considerably different effects on expression of hepatic microsomal monooxygenases than the relatively selective induction of CYP2E1 observed following consumption of...

  17. Alcohol-Impaired Speed and Accuracy of Cognitive Functions: A Review of Acute Tolerance and Recovery of Cognitive Performance

    Microsoft Academic Search

    Tom A. Schweizer; Muriel Vogel-Sprott

    2008-01-01

    Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews

  18. Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Alcoholic hepatitis is the most florid presentation of alcohol-related liver disease. In its severe form, defined by a Maddrey’s discriminant function (DF) ?32, the 28-day mortality rate is approximately 35%. A number of potential treatments have been subjected to clinical trials, of which two, corticosteroids and pentoxifylline, may have therapeutic benefit. The role of corticosteroids is controversial as trial results have been inconsistent, whereas the role of pentoxifylline requires confirmation as only one previous placebo-controlled trial has been published. Methods/design STOPAH is a multicentre, double-blind, factorial (2 × 2) trial in which patients are randomised to one of four groups: 1. Group A: placebo / placebo 2. Group B: placebo / prednisolone 3. Group C: pentoxifylline / placebo 4. Group D: pentoxifylline / prednisolone The trial aims to randomise 1,200 patients with severe alcoholic hepatitis, in order to provide sufficient power to determine whether either of the two interventions is effective. The primary endpoint of the study is mortality at 28 days, with secondary endpoints being mortality at 90 days and 1 year. Discussion STOPAH aims to be a definitive study to resolve controversy around the existing treatments for alcoholic hepatitis. Eligibility criteria are based on clinical parameters rather than liver biopsy, which are aligned with standard clinical practice in most hospitals. The use of a factorial design will allow two treatments to be evaluated in parallel, with efficient use of patient numbers to achieve high statistical power. Trial registration EudraCT reference number: 2009-013897-42 ISRCTN reference number: ISRCTN88782125 PMID:23958271

  19. MATERNAL COFFEE AND ALCOHOL CONSUMPTION DURING PREGNANCY, PARENTAL SMOKING AND RISK OF CHILDHOOH ACUTE LEUKEMIA

    E-print Network

    Paris-Sud XI, Université de

    ACUTE LEUKEMIA Short title: Maternal coffee and alcohol consumption, parental smoking and childhood leukemia Category : Original article Condensed abstract : Maternal habits during pregnancy, as maternal smoking and maternal beverage consumption, were obtained for 280 cases of childhood acute leukemia and 280

  20. Acute hypoxia and cytochrome P450–mediated hepatic drug metabolism in humans

    Microsoft Academic Search

    Gesche Jürgens; Hanne Rolighed Christensen; Kim Brøsen; Jesper Sonne; Steffen Loft; Niels Vidiendal Olsen

    2002-01-01

    Objective: Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.Methods: Twelve healthy subjects who lived at sea level were exposed to altitude-induced hypoxia for 7 days at 4559 m above sea level. Hepatic CYP enzyme activity was measured before departure, at 24 and 96 hours after arrival to high-altitude location,

  1. Lamivudine treatment for acute severe hepatitis B: report of a case and review of the literature.

    PubMed

    Roussos, A; Koilakou, S; Kalafatas, I; Kalantzis, C; Apostolou, N; Grivas, E; Raptis, N; Mantzaris, G

    2008-01-01

    The oral nucleoside analogue lamivudine has been effectively used in the treatment of chronic hepatitis B. However, there is limited data concerning the efficacy and safety of lamivudine in patients with severe acute or fulminant hepatitis B. We report the use of lamivudine in a young woman with acute HBV infection and fulminant hepatic failure. Following lamivudine treatment, we noticed a prompt clinical, biochemical, serological and virological response as it was seen in the vast majority of, previously reported, cases. Lamivudine treatment was continued until HBsAg was cleared. Our case, as well as previously reported ones, suggests that lamivudine may have a beneficial effect in selected patients with acute severe or fulminant HBV infection. PMID:18396747

  2. Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion.

    PubMed Central

    Tsai, S L; Chen, P J; Lai, M Y; Yang, P M; Sung, J L; Huang, J H; Hwang, L H; Chang, T H; Chen, D S

    1992-01-01

    T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preS1), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P less than 0.001 and P less than 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P less than 0.05 and P less than 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS1 either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two- to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations. Images PMID:1729285

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

    SciTech Connect

    Lieber, Charles S. [Section of Liver Diseases, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY (United States)], E-mail: liebercs@aol.com; Leo, Maria A. [Section of Liver Diseases, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY (United States); Wang Xiaolei [Department of Medicine, Mount Sinai School of Medicine, New York, NY (United States); DeCarli, Leonore M. [Section of Liver Diseases, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States)

    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.

  4. Acute Alcohol Consumption Disrupts the Hormonal Milieu of Lactating Women

    Microsoft Academic Search

    Julie A. Mennella; M. Yanina Pepino; Karen L. Teff

    Despite the lack of scientific evidence to support the claim that alcohol is a galactagogue, lactating women have been advisedtodrinkalcoholasanaidtolactationforcenturies.To test the hypothesis that alcohol consumption affects the hor- monal response in lactating women, we conducted a within- subjects design study in which 17 women consumed a 0.4 g\\/kg dose of alcohol in orange juice during one test session and

  5. Absence of Perilipin 2 Prevents Hepatic Steatosis, Glucose Intolerance and Ceramide Accumulation in Alcohol-Fed Mice

    PubMed Central

    Carr, Rotonya M.; Peralta, Giselle; Yin, Xiaoyan; Ahima, Rexford S.

    2014-01-01

    Background Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of steatosis, glucose intolerance, and ceramide accumulation in alcoholic liver disease. We investigated the role of Plin2 on energy balance and glucose and lipid homeostasis in wildtype and Plin2 knockout (Plin2KO) mice chronically fed a Lieber-DeCarli liquid ethanol or control diet for six weeks. Methods We performed in vivo measurements of energy intake and expenditure; body composition; and glucose tolerance. After sacrifice, liver was dissected for histology and lipid analysis. Results We found that neither genotype nor diet had a significant effect on final weight, body composition, or energy intake between WT and Plin2KO mice fed alcohol or control diets. Additionally, alcohol feeding did not affect oxygen consumption or carbon dioxide production in Plin2KO mice. We performed glucose tolerance testing and observed that alcohol feeding failed to impair glucose tolerance in Plin2KO mice. Most notably, absence of Plin2 prevented hepatic steatosis and ceramide accumulation in alcohol-fed mice. These changes were related to downregulation of genes involved in lipogenesis and triglyceride synthesis. Conclusions Plin2KO mice chronically fed alcohol are protected from hepatic steatosis, glucose intolerance, and hepatic ceramide accumulation, suggesting a critical pathogenic role of Plin2 in experimental alcoholic liver disease. PMID:24831094

  6. Acute alcohol response phenotype in heavy social drinkers is robust and reproducible

    PubMed Central

    Roche, Daniel J.O.; Palmeri, Michael D.; King, Andrea C.

    2014-01-01

    Background In three previously published works (Brumback et al., 2007; King et al., 2011a; Roche and King 2010), our group characterized acute alcohol responses in a large group of young, heavy binge drinkers (n = 104) across a variety of subjective, eye tracking, and psychometric performance measures. Methods The primary goal of the current study was to directly replicate prior findings of alcohol response in heavy social drinkers in a second independent cohort (n = 104) using identical methodology. A secondary goal was to examine the effects of family history of alcohol use disorders on acute alcohol response in both samples. Participants attended two randomized laboratory sessions in which they consumed 0.8 g/kg alcohol or a taste-masked placebo. At preand post-drink time points, participants completed subjective scales, psychomotor performance and eye movement tasks, and provided salivary samples for cortisol determination. Results Results showed that the second cohort of heavy drinkers exhibited a nearly identical pattern of alcohol responses to the original cohort, including sensitivity to alcohol’s stimulating and hedonically rewarding effects during the rising BrAC limb, increases sedation during the declining BrAC limb, a lack of cortisol response, and psychomotor and eye tracking impairment that was most evident at peak BrAC. The magnitude and temporal pattern of these acute effects of alcohol in the second cohort were similar to the first cohort across all measures, with the exception of three eye movement measures: pro- and anti-saccade accuracy and anti-saccade velocity. Family history of alcohol use disorders did not affect alcohol response in the first cohort and this was replicated in the second cohort. Conclusions In sum, in two independent samples, we have demonstrated that heavy social drinkers display a consistent and reliable sensitivity to alcohol’s subjective effects and impairment of eye tracking and psychomotor performance, which is not affected by family history status. This acute alcohol response phenotype in heavy, frequent binge drinkers appears to be robust and reproducible. PMID:24117681

  7. Curative effect of lauromacrogol and absolute ethyl alcohol injection guided by ultrasound on simplex hepatic cyst.

    PubMed

    Xue, Jie; Geng, Xianhui

    2015-03-01

    This research aims to analyze the curative effect and security of lauromacrogol injection and absolute ethyl alcohol treating simplex hepatic cyst respectively. The simplex hepatic cyst patients were divided into lauromacrogol group (86 cases, research group) and absolute ethyl alcohol group (80 cases, control group). Both two groups received sclerotherapy of thoracic drainage under ultrasonic guidance and the curative effect and untoward effect were observed. The result showed there was no hemorrhage or infection within two groups. During the therapeutic process, 45 patients (56.3%) suffered from pain at different degrees and 23 cases were found with symptom of drunkenness in control group, while the patients in the research group were found with no obvious discomfort. A week after treatment, 23 patients (25.0%) in control group still remained to have swelling pain at upper right stomach, while there were only 9 in treatment group (10.5%), and the difference was of statistical significance (X(2)=6.037, P<0.05). through 6 months of follow-up visit after the operation, we found the cure rate of lauromacrogol group was 94.6% and absolute ethyl alcohol was 92.6%, and the difference between these two groups was of no statistical significance (P>0.05). The results showed that, in the treatment of cystosclerosis with absolute ethyl alcohol injection under ultrasonic guidance, some patients suffered pain and the symptom of drunkenness at different degrees, whereas, lauromacrogol was effective with no untoward effects, therefore it is worthy of clinical popularization and application. PMID:25796160

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

    PubMed

    Marshall, Stephanie M; Gromovsky, Anthony D; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

    2014-01-01

    The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ? 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion. PMID:24901470

  9. Aminotransferase changes and acute hepatitis in patients with dengue fever: analysis of 1,585 cases

    Microsoft Academic Search

    Luiz José de Souza; José Galvão Alves; Rita Maria Ribeiro Nogueira; Carlos Gicovate Neto; Diogo Assed Bastos; Edno Wallace da Silva Siqueira; João Tadeu Damian Souto Filho; Thiago de Abreu Cezário; Carlos Eduardo Soares; Rodrigo da Costa Carneiro

    2004-01-01

    Introduction: Type 3 dengue virus caused an extensive epidemic in the state of Rio de Janeiro in summer 2002. In some of the patients, it was found in an atypical form with increased aminotransferase levels and acute hepatitis. Material and Methods: An analysis was made of 1,585 serologically confirmed dengue cases at the Dengue Reference Center in Campos dos Goytacazes,

  10. Massive Infiltration of Liver by Metastatic Adenocarcinoma: A Rare Cause of Acute Hepatic Failure

    PubMed Central

    Varghese, Joy; Jayanthi, Venkataraman; Patra, Susma; Rela, Mohamed

    2012-01-01

    Acute liver cell failure can occur by diffuse infiltration of malignant cells in liver parenchyma. The malignant cells might be either primary hepatocellular carcinoma or metastatic liver disease. Mostly, CT abdomen with intravenous contrast fails to detect liver malignancy. We report a case of liver metastasis masquerading as fulminant hepatic failure.

  11. 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 ...

  12. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

    PubMed Central

    Li, Jian; Niu, Jian-Zhao; Wang, Ji-Feng; Li, Yu; Tao, Xiao-Hua

    2005-01-01

    AIM: To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS: Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-?m thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS: The diameter (2.207 ± 0.096 vs 1.528 ± 0.054 mm, P<0.01) and pressure (11.014±0.395 vs 8.533±0.274 mmHg, P<0.01) of portal vein were significantly higher in model group than those in the control group. Plasma HA (129.97±16.10 vs 73.09±2.38 ng/mL, P<0.01), ColIV (210.49±4.36 vs 89.65±4.42 ng/mL, P<0.01) and LN (105.00±7.29 vs 55.70±4.32 ng/mL, P<0.01) were upregulated in model group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased remarkably and perisinusoids were almost surrounded by ColIII. Immunohistochemical staining showed that ColIV protein level (0.130±0.007 vs 0.032±0.004, P<0.01) and LN protein level (0.152±0.005 vs 0.029±0.005, P<0.01) were up-regulated remarkably in model group. MMP-2 protein expression (2.306±1.089 vs 0.612±0.081, P<0.01) and TIMP-1 protein expression (3.015±1.364 vs 0.446±0.009, P<0.01) in freshly isolated hepatic non-parenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669±0.170 vs 1.695±0.008, P<0.05). CONCLUSION: Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcohol-induced portal hypertension in rats. PMID:16425420

  13. The acute effects of alcohol on auditory thresholds

    Microsoft Academic Search

    Tahwinder Upile; Fabian Sipaul; Waseem Jerjes; Sandeep Singh; Seyed Ahmad Reza Nouraei; Mohammed El Maaytah; Peter Andrews; John Graham; Colin Hopper; Anthony Wright

    2007-01-01

    BACKGROUND: There is very little knowledge about alcohol-induced hearing loss. Alcohol consumption and tolerance to loud noise is a well observed phenomenon as seen in the Western world where parties get noisier by the hour as the evening matures. This leads to increase in the referrals to the \\

  14. Acute effects of alcohol on the human brain: a resting-state FMRI study.

    PubMed

    Zheng, Hongyi; Kong, Lingmei; Chen, Lanmei; Zhang, Haidu; Zheng, Wenbin

    2015-01-01

    The aim of this study is to assess the value of resting-state fMRI in detecting the acute effects of alcohol on healthy human brains. Thirty-two healthy volunteers were studied by conventional MR imaging and resting-state fMRI prior to and 0.5 hours after initiation of acute alcohol administration. The fMRI data, acquired during the resting state, were correlated with different breath alcohol concentrations (BrAC). We use the posterior cingulate cortex/precuneus as a seed for the default mode network (DMN) analysis. ALFF and ReHo were also used to investigate spontaneous neural activity in the resting state. Conventional MR imaging showed no abnormalities on all subjects. Compared with the prior alcohol administration, the ALFF and ReHo also indicated some specific brain regions which are affected by alcohol, including the superior frontal gyrus, cerebellum, hippocampal gyrus, left basal ganglia, and right internal capsule. Functional connectivity of the DMN was affected by alcohol. This resting-state fMRI indicates that brain regions implicated are affected by alcohol and might provide a neural basis for alcohol's effects on behavioral performance. PMID:25705701

  15. Acute Effects of Alcohol on the Human Brain: A Resting-State fMRI Study

    PubMed Central

    Zheng, Hongyi; Kong, Lingmei; Chen, Lanmei; Zhang, Haidu

    2015-01-01

    The aim of this study is to assess the value of resting-state fMRI in detecting the acute effects of alcohol on healthy human brains. Thirty-two healthy volunteers were studied by conventional MR imaging and resting-state fMRI prior to and 0.5 hours after initiation of acute alcohol administration. The fMRI data, acquired during the resting state, were correlated with different breath alcohol concentrations (BrAC). We use the posterior cingulate cortex/precuneus as a seed for the default mode network (DMN) analysis. ALFF and ReHo were also used to investigate spontaneous neural activity in the resting state. Conventional MR imaging showed no abnormalities on all subjects. Compared with the prior alcohol administration, the ALFF and ReHo also indicated some specific brain regions which are affected by alcohol, including the superior frontal gyrus, cerebellum, hippocampal gyrus, left basal ganglia, and right internal capsule. Functional connectivity of the DMN was affected by alcohol. This resting-state fMRI indicates that brain regions implicated are affected by alcohol and might provide a neural basis for alcohol's effects on behavioral performance. PMID:25705701

  16. 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

  17. 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

  18. Factors Associated with Alcohol Consumption in Hepatitis B Carriers: A Nationwide Study in the Republic of Korea

    PubMed Central

    Park, Boyoung; Jung, Kyu-Won; Oh, Chang-Mo; Choi, Kui Son; Suh, Mina; Jun, Jae Kwan

    2014-01-01

    This study was conducted to investigate the prevalence of alcohol consumption and identify the sociodemographic factors associated with alcohol consumption among individuals with hepatitis B virus(HBV) infection. We used data from the Korean National Health and Nutrition Examination Surveys, a nationwide survey conducted between 2007 and 2011. “Monthly alcohol consumption” was defined as having consumed alcohol at least once per month during the past year, and “high-risk alcohol consumption” was defined as having consumed alcohol twice or more per week and, for males, having consumed at least 60 g of alcohol on one occasion or, for females, having consumed at least 40 g of alcohol on more than one occasion. The prevalence of monthly alcohol consumption was 53.2%, and that of high-risk alcohol consumption was 11.8% among HBV carriers. Less education was associated with both monthly and high-risk alcohol consumption(OR?=?1.75 [95% CI?=?1.02?3.02] for monthly alcohol consumption among those with less than a high school education; OR?=?2.48 [95% CI?=?1.19?5.17] for high-risk alcohol consumption among those with less than a high school education and OR?=?2.02 [95% CI?=?1.12?3.64] among those with a high school education). Additionally, smoking and being male increased the risk of alcohol consumption, and older age and having a normal body mass index decreased the risk. HBV carriers who were less educated, overweight, and smokers were more likely to consume alcohol or meet criteria for high-risk drinking. Health policies and intervention programs aimed at promoting a generally healthy lifestyle in HBV carriers should consider educational inequalities and alcohol consumption. PMID:25387237

  19. Influences of Situational Factors and Alcohol Expectancies on Sexual Desire and Arousal Among Heavy-Episodic Drinking Women: Acute Alcohol Intoxication and Condom Availability

    PubMed Central

    George, William H.; Nguyen, Hong V.; Heiman, Julia R.; Davis, Kelly Cue; Norris, Jeanette

    2013-01-01

    Although studies suggest that alcohol increases women’s sexual desire, no studies to our knowledge have examined the effects of acute alcohol intoxication on women’s sexual desire. The majority of research examining alcohol’s effects on sexual arousal in women suggests that alcohol increases self-reported arousal. In an alcohol administration study in which women projected themselves into an eroticized scenario depicting a consensual sexual encounter with a new male partner, we examined the effects of alcohol and condom condition on women’s sexual desire and arousal. The moderating effects of sex-related alcohol expectancies were also examined. Results revealed that alcohol intoxication was related to less desire to engage in sex with a new partner and condom presence was related to more desire. Alcohol interacted with sexual disinhibition alcohol expectancies, indicating that more expectancy endorsement was associated with greater sexual desire and self-reported arousal in the alcohol condition, but not the control condition. Condom condition had no effect on self-reported sexual arousal. The present research suggests that sexual desire merits research attention in non-clinical samples, and experimental methodology can provide valuable information about alcohol’s influence on women’s sexual desire, thus advancing our understanding of this relationship beyond cross-sectional correlations. The current findings also provide evidence that sex-related alcohol expectancies may play an important role in alcohol-involved sexual experiences including desire and arousal. PMID:23661324

  20. A case of acute autoimmune hepatitis presenting after incomplete-type CREST syndrome and chronic thyroiditis.

    PubMed

    Himoto, Takashi; Nomura, Takako; Tani, Joji; Miyoshi, Hisaaki; Morishita, Asahiro; Yoneyama, Hirohito; Kurokohchi, Kazutaka; Kushida, Yoshio; Watanabe, Seishiro; Masaki, Tsutomu

    2014-09-01

    A 55-year-old woman was admitted to our hospital with acute hepatitis of unknown origin. She had a history of incomplete-type CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and chronic thyroiditis approximately 10 years earlier. Although she achieved spontaneous remission without treatment, she was re-admitted 18 months later due to recurrent liver dysfunction. Liver biopsy was performed as we strongly suspected autoimmune hepatitis despite her normal serum immunoglobulin G level. Liver biopsy findings were histologically compatible with autoimmune hepatitis, and administering prednisolone (30 mg/day) led to a prompt recovery of her liver dysfunction. No relapse occurred during the tapering of prednisolone to a maintenance dose of 5 mg/day. Here we report a rare case of autoimmune hepatitis in a patient with a history of incomplete-type CREST syndrome and chronic thyroiditis. PMID:25195969

  1. Acute hepatitis in a young woman with systemic lupus erythematosus: a diagnostic challenge

    PubMed Central

    Barosa, Rita; Ramos, Lídia Roque; Fonseca, Cristina; Freitas, João

    2013-01-01

    A 48-year-old woman with systemic lupus erythematosus diagnosis was on naproxen, hidroxichloroquine and acetylsalicylic acid. She had self-suspended all medication and resumed 1?year later. Five days after the medication was resumed, she developed acute hepatitis, with biochemical hepatic cytolysis, hypergamaglobulinaemia and a serum antinuclear antibody titre of 1/2560. Idiopathic autoimmune hepatitis was considered, but drug-induced liver injury could not definitely be ruled out. Patient declined liver biopsy. Oral prednisolone was started. Within 3?months with prednisolone being tapered to 10?mg/day, a new flare occurred. Liver biopsy was performed and it favoured autoimmune hepatitis diagnosis. We discuss the diagnostic options and treatment approach in a patient with autoimmune disease and possible drug-induced liver injury who initially declined liver biopsy. PMID:23563681

  2. 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 ?-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 ?-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-1?, 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.

  3. Guillain-Barré Syndrome Associated with Acute HEV Hepatitis

    Microsoft Academic Search

    Rawshan Ara Khanam; Mohammad Omar Faruq; Rawshan Ali Basunia; ASM Areef Ahsan

    2009-01-01

    Guillain-Barré Syndrome (GBS) otherwise known as Acute Inflammatory Polyneuritis, characterized by acute progressive limb weakness and aretlexia, is the prototype of a post infectious autoimmune disease. Two-thirds of the cases of GBS emerge from viral or bacterial infection. In August 2006, a 20 year old man presented at ICU, BIRDEM Hospital with a history of brief icteric illness followed by

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

    PubMed

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

    2014-07-01

    Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera. PMID:25073673

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

    Microsoft Academic Search

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

    Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data\\u000a investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance,\\u000a and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed\\u000a this 20-day within-participant, residential laboratory study. During four

  6. Ramadan fasting triggering koro-like symptoms during acute alcohol withdrawal: a case report from Oman.

    PubMed

    Al-Sinawi, Hamed; Al-Adawi, Samir; Al-Guenedi, Amr

    2008-12-01

    This article describes a case of koro-like symptoms from Oman associated with alcohol withdrawal and illustrates how the socio-cultural practices of Ramadan-fasting affected the patterning and timing of presentation of severe alcohol withdrawal symptoms. The patient was severely distressed by the delusion that his penis had been amputated. The acute anxiety involving this delusion appears to be conceptually and phenomenologically similar to koro. PMID:19091733

  7. 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

  8. Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

    PubMed Central

    2010-01-01

    Background Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications. Case presentation Here we describe a case of hepatic artery thrombosis after living-donor liver transplantation which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-transplantation the patient recovered without sequelae. Conclusion This case highlights the need to remain cautious when psychiatric disorders occur in patients after liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of psychosis alone but should also focus vascular complications related to orthotopic liver transplantation. PMID:20175918

  9. Assessment of alcohol consumption among hepatitis C-positive people receiving opioid maintenance treatment using direct ethanol metabolites and self-report: a pilot study.

    PubMed

    Wurst, Friedrich M; Haber, Paul S; Wiesbeck, Gerhard; Watson, Bianca; Wallace, Cate; Whitfield, John B; Halter, Claudia; Weinmann, Wolfgang; Conigrave, Katherine M

    2008-09-01

    This study was conducted to identify the alcohol consumption among hepatitis C-positive people receiving opioid maintenance therapy using self-report and biomarkers. A total of 49 people (28 male, 21 female) were hepatitis C virus (HCV) positive and were included. The alcohol use disorder identification test (AUDIT) and self-reported ethanol intake in the last 28 days were assessed. In addition to gamma-glutamyl-transferase (GGT) and mean corpuscular volume (MCV), ethyl glucuronide (EtG) and ethyl sulphate (EtS) were determined in serum and urine (UEtG, UEtS, SEtG) using liquid chromatography/tandem mass-spectroscopy (LC/MS-MS) with deuterated internal standards. Abstinence from alcohol was reported for the last 28 days by 13 participants and for the last 7 days by 22. AUDIT was > 8 in 27 cases. The maximum values were 34.8 mg/l for UEtG, 5.3 mg/l for UEtS and 0.15 for SEtG. Among the 19 UEtG positives, 8 had not reported any ethanol intake in the 7 days prior to the study. Six participants reported intake of up to 320 g of ethanol in the last 7 days, but were negative for SEtG, UEtG and UEtS. Self-reported ethanol intake in the last 28 days correlated with AUDIT score (r = 0.733, P < 0.001), with the direct ethanol metabolites and MCV. In this population, abstinence and episodic heavy drinking are more common than in the general population. Episodic heavy drinking is a significant cause of acute risk in this population. Results from biomarker testing could indicate cases of under- as well as over-reporting of alcohol consumption. Further research on the diagnostic accuracy of direct ethanol metabolites, including the use of phosphatidylethanol (PEth), in this setting is needed. PMID:17711559

  10. Percutaneous Alcohol Sclerotherapy of Simple Hepatic Cysts. Results From a Multicentre Survey in Italy

    PubMed Central

    Montorsi, Marco; Torzilli, Guido; Fumagalli, Uberto; Bona, Stefano; Rosati, Riccardo; de Simone, Matilde; Rovati, Vittorio; Mosca, Franco; Filice, Carlo

    1994-01-01

    The increased use of Ultrasonography (US) has led to increased detection of simple hepatic cysts. For symptomatic cysts treatment is necessary. Until some years ago surgery was the only therapy. We have treated a large number of patients with Percutaneous Alcohol Sclerotherapy (PAS) and evaluated retrospectively the efficacy of this approach. Data on 21 patients with symptomatic simple hepatic cysts were reviewed retrospectively. Cysts had a mean diameter of 9 cm (range: 7–15 cm). PAS was always performed under local anesthesia and US guidance. 25% of the volume was replaced with 95% ethanol and then completely aspirated after 20–30 minutes. No complications or deaths occurred. In all patients symptoms disappeared after treatment. In 15 out of 21 cases there was no evidence of residual cyst on US, computed tomography (CT) or magnetic resonance (MRI). In 6 patients with shorter follow-up, cysts showed a mean reduction in diameter of 50%. The mean follow-up was 18 months (range 6–60 months). We conclude that PAS is easy with low risk for the patients and with good long-term results; it should therefore become the procedure of choice for simple hepatic cysts. PMID:7880778

  11. Hepatitis

    MedlinePLUS

    ... to a liver condition called hepatitis . What Is Hepatitis? The liver is one of the body's powerhouses. ... option that is not always available or successful. Hepatitis A The hepatitis A virus (HAV) is transmitted ...

  12. Hepatitis

    MedlinePLUS

    ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ... the most common types of viral hepatitis. Continue Hepatitis A For kids, hep A is the most ...

  13. Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis.

    PubMed

    Støy, Sidsel; Dige, Anders; Sandahl, Thomas Damgaard; Laursen, Tea Lund; Buus, Christian; Hokland, Marianne; Vilstrup, Hendrik

    2015-02-15

    The dynamics and role of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and NKT cells in the life-threatening inflammatory disease alcoholic hepatitis is largely unknown. These cells directly kill infected and damaged cells through, e.g., degranulation and interferon-? (IFN?) production, but cause tissue damage if overactivated. They also assist tissue repair via IL-22 production. We, therefore, aimed to investigate the frequency, functionality, and activation state of such cells in alcoholic hepatitis. We analyzed blood samples from 24 severe alcoholic hepatitis patients followed for 30 days after diagnosis. Ten healthy abstinent volunteers and 10 stable abstinent alcoholic cirrhosis patients were controls. Using flow cytometry we assessed cell frequencies, NK cell degranulation capacity following K562 cell stimulation, activation by natural killer group 2 D (NKG2D) expression, and IL-22 and IFN? production. In alcoholic hepatitis we found a decreased frequency of CTLs compared with healthy controls (P < 0.001) and a similar trend for NK cells (P = 0.089). The NK cell degranulation capacity was reduced by 25% compared with healthy controls (P = 0.02) and by 50% compared with cirrhosis patients (P = 0.04). Accordingly, the NKG2D receptor expression was markedly decreased on NK cells, CTLs, and NKT cells (P < 0.05, all). The frequencies of IL-22-producing CTLs and NK cells were doubled compared with healthy controls (P < 0.05, all) but not different from cirrhosis patients. This exploratory study for the first time showed impaired cellular cytotoxicity and activation in alcoholic hepatitis. This is unlikely to cause hepatocyte death but may contribute toward the severe immune incompetence. The results warrant detailed and mechanistic studies. PMID:25501547

  14. Alcohol, smoking, coffee and risk of non-fatal acute myocardial infarction in Italy

    Microsoft Academic Search

    Alessandra Tavani; Michaela Bertuzzi; Eva Negri; Loredana Sorbara; Carlo La Vecchia

    2001-01-01

    Objectives: To assess the relation between cigarette smoking, alcohol, coffee, decaffeinated coffee and tea consumption, and the risk of non-fatal acute myocardial infarction (AMI). Design and setting: Hospital-based case–control study conducted in 1995–1999 in Milan, Italy. Patients: 507 cases with a first episode of non-fatal AMI, and 478 controls admitted to hospital for acute diseases. Methods: Information was collected by

  15. Proinflammatory Cytokines in Alcohol or Gallstone Induced Acute Pancreatitis. A Prospective Study

    Microsoft Academic Search

    Srdan Novovic; Anders Møller Andersen; Annette Kjær Ersbøll; Ole Haagen Nielsen; Lars Nannestad Jorgensen; Mark Berner Hansen

    Objectives If differences of inflammatory pathways in acute pancreatitis exist for various etiologies, selective and specific anti- inflammatory and other modulatory treatment regimens might be indicated. Circulating levels of prominent proinflammatory cytokines IL-6, 8, 18, and TNF-alpha were measured in patients having their first attack of either alcohol- or gallstone-induced acute pancreatitis. Methods Seventy-five consecutive patients were prospectively included over

  16. Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1? 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-? coactivator-1? (PGC-1?), 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-1? overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1? 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-1?. PMID:24091599

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

    SciTech Connect

    Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China) [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China)] [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China) [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

    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.

  18. Acute Alcohol Effects on Attentional Bias in Heavy and Moderate Drinkers

    PubMed Central

    Weafer, Jessica; Fillmore, Mark T.

    2012-01-01

    Heavy drinkers show an increased attentional bias to alcohol-related stimuli compared to moderate drinkers, and this bias is thought to promote motivation for alcohol consumption (Field & Cox, 2008). Studies have begun to examine acute alcohol effects on attentional bias, however little is known regarding how these effects might differ based on drinker type. Further, the degree to which attentional bias in response to alcohol is associated with excessive alcohol consumption remains unexplored. For the current study, 20 heavy drinkers and 20 moderate drinkers completed a visual probe task in response to placebo and two active doses of alcohol (0.45 g/kg and 0.65 g/kg). Participants’ eye-movements were monitored and attentional bias was calculated as the difference in time spent focused on alcohol compared to neutral images. Participants’ alcohol consumption was assessed by a timeline follow-back calendar and a laboratory ad lib consumption task. Results showed that heavy drinkers displayed significantly greater attentional bias than did moderate drinkers following placebo. However, heavy drinkers displayed a dose-dependent decrease in attentional bias following alcohol, whereas the drug had no effect in moderate drinkers. Individual differences in attentional bias under placebo were strongly associated with both self-reported and laboratory alcohol consumption, yet bias following alcohol administration did not predict either measure of consumption. These findings suggest that attentional bias is strongest before a drinking episode begins. As such, an attentional bias might be most influential in terms of initiation of alcohol consumption, and less of a factor in promoting continued consumption within the drinking episode. PMID:22732051

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

    PubMed Central

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

    2006-01-01

    AIM: To asses the expression of myeloid dendritic cells (CD11c+) subset during acute HCV hepatitis and its possible involvement in natural history of the infection. METHODS: We enrolled 11 patients with acute hepatitis C (AHC) (Group A), 10 patients with acute hepatitis A (AHA) (as infective control-Group B) and 10 healthy donors (group C) in this study. All patients underwent selective flow cytometry gating strategies to assess the peripheral number of the myeloid dendritic cells (mDCs) to understand the possible role and differences during acute hepatitis. RESULTS: Eight of 11 patients with acute HCV hepatitis did not show any increase of mDCs compared to healthy individuals, while a significant decrease of mDCs was found in absolute cell count (z?=?-2.37; P?acute infection, resolved the illness. CONCLUSION: The lack of increase of mDCs during acute hepatitis C might be an important factor involved in chronicization of the infection. PMID:16534853

  20. [A case of acute autoimmune hepatitis associated with autoimmune hemolytic anemia].

    PubMed

    Hanai, Tatsunori; Naiki, Takafumi; Takamatsu, Manabu; Imai, Kenji; Kitagawa, Junichi; Suetsugu, Atsushi; Takai, Koji; Shiraki, Makoto; Shimizu, Masahito; Hirose, Yoshinobu; Tsurumi, Hisashi; Moriwaki, Hisataka

    2013-10-01

    A 61-year-old female was admitted to our hospital with severe jaundice and anemia. She was diagnosed with severe acute hepatitis secondary to autoimmune hepatitis (AIH) on the basis of positive anti-nuclear antibody titers, high serum IgG levels, and liver biopsy. Autoimmune hemolytic anemia (AIHA) was diagnosed because of the presence of reticulocytosis, decreased haptoglobin, positive direct Coombs test, and erythroid hyperplasia in the bone marrow. Although AIH occurs in association with various immunological disorders, an association with AIHA is rarely reported. We report a rare case of severe AIH associated with AIHA. PMID:24097153

  1. 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)...

  2. Influences of situational factors and alcohol expectancies on sexual desire and arousal among heavy-episodic drinking women: acute alcohol intoxication and condom availability.

    PubMed

    Gilmore, Amanda K; George, William H; Nguyen, Hong V; Heiman, Julia R; Davis, Kelly Cue; Norris, Jeanette

    2013-08-01

    Although studies suggest that alcohol increases women's sexual desire, no studies to our knowledge have examined the effects of acute alcohol intoxication on women's sexual desire. The majority of research examining alcohol's effects on sexual arousal in women suggests that alcohol increases self-reported arousal. In an alcohol administration study in which women projected themselves into an eroticized scenario depicting a consensual sexual encounter with a new male partner, we examined the effects of alcohol and condom condition on women's sexual desire and arousal. The moderating effects of sex-related alcohol expectancies were also examined. Results revealed that alcohol intoxication was related to less desire to engage in sex with a new partner and condom presence was related to more desire. Alcohol interacted with sexual disinhibition alcohol expectancies, indicating that more expectancy endorsement was associated with greater sexual desire and self-reported arousal in the alcohol condition, but not the control condition. Condom condition had no effect on self-reported sexual arousal. The present research suggests that sexual desire merits research attention in non-clinical samples, and experimental methodology can provide valuable information about alcohol's influence on women's sexual desire, thus advancing our understanding of this relationship beyond cross-sectional correlations. The current findings also provide evidence that sex-related alcohol expectancies may play an important role in alcohol-involved sexual experiences including desire and arousal. PMID:23661324

  3. 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…

  4. Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations

    E-print Network

    Kalueff, Allan V.

    Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations Robert Gerlai, Fahad Ahmad, and Sonal Prajapati Background: With the arsenal of genetic tools available for zebrafish developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing

  5. A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

    PubMed

    Baek, Hyun Seok; Lee, Se-Jin

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. PMID:25578790

  6. 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

  7. HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain

    Microsoft Academic Search

    Sonia Pina; Maria Buti; Montserrat Cotrina; Joan Piella; Rosina Girones

    2000-01-01

    Background\\/Aims: Hepatitis E virus (HEV) is an enterically transmitted pathogen that appears sporadically in non-endemic countries. We studied HEV as a causal agent of acute hepatitis cases in the Spanish population, and the role of pigs as an animal reservoir.Methods: The presence of HEV-RNA was analysed by nested polymerase chain reaction in 37 serum samples from patients with acute viral

  8. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a procedure to determine motor effects by alcohol across the lifespan. PMID:25613215

  9. [A case report of alverine-citrate-induced acute hepatitis].

    PubMed

    Han, Jee Young; Lee, Jin Woo; Kim, Joon Mee; Joo, Kowoon; Chon, Ung; Lee, Jung Il; Jeong, Seok; Lee, Don Haeng; Kim, Young Soo; Min, Kyung Sun

    2010-03-01

    Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity. PMID:20375645

  10. Differentiation of acute and chronic hepatitis B in IgM anti-HBc positive patients

    PubMed Central

    Park, Ji Won; Kwak, Kyeong Min; Kim, Sung Eun; Jang, Myoung Kuk; Kim, Dong Joon; Lee, Myung Seok; Kim, Hyoung Su; Park, Choong Kee

    2015-01-01

    AIM: To identify the factors that differentiate acute hepatitis B (AHB) from chronic hepatitis B with acute exacerbation (CHB-AE). METHODS: From 2004 to 2013, a total of 82 patients (male n = 52, 63.4%; female n = 30, 36.6%) with clinical features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B core antigen (IgM anti-HBc) were retrospectively enrolled and divided into two groups; AHB (n = 53) and CHB-AE (n = 29). The AHB group was defined as patients without a history of hepatitis B virus (HBV) infection before the episode and with loss of hepatitis B surface antigen within 6 mo after onset of acute hepatitis. Biochemical and virological profiles and the sample/cutoff (S/CO) ratio of IgM anti-HBc were compared to determine the differential diagnostic factors. RESULTS: The multivariate analysis demonstrated that, the S/CO ratio of IgM anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of IgM anti-HBc was significantly higher in the AHB group, while the HBV DNA level was significantly higher in the CHB-AE group. The optimal cutoff values of IgM anti-HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio and 5.5 log10 IU/mL, respectively. The sensitivity and specificity were 96.2% and 89.7% for the S/CO ratio of IgM anti-HBc and 81.1% and 72.4% for HBV DNA levels, respectively. The area under receiver operating characteristic curves of both the S/CO ratio of IgM anti-HBc and HBV DNA levels were not significantly different (0.933 vs 0.844, P = 0.105). When combining IgM anti-HBc and HBV DNA, the diagnostic power significantly improved compared to HBV DNA alone (P = 0.0056). The combination of these factors yielded a sensitivity and specificity of 98.1% and 86.2%, respectively. CONCLUSION: The combination of the S/CO ratio of IgM anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE in patients with positive IgM anti-HBc.

  11. Diabetes increases the risk of acute hepatic failure

    Microsoft Academic Search

    James E. Everhart

    2002-01-01

    Background & Aims: It is unclear whether patients with diabetes are at an increased risk of developing acute liver failure (ALF). We performed a large cohort study to examine the occurrence of ALF by using the databases of the Department of Veterans Affairs. Methods: We identified all patients with a hospital discharge diagnosis of diabetes (ICD-9 codes: 250 [1–9][0–4]) from

  12. 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

  13. Clinical features of acute viral hepatitis B in Korea: a multi-center study

    PubMed Central

    Choi, Hye Jin; Choe, Won Hyeok; Seo, Yeon Seok; Kim, Ji Hoon; Byun, Kwan Soo; Kim, Young Seok; Kim, Seung Up; Baik, Soon Koo; Cheong, Jae Youn; Kim, Tae Yeob; Kwon, Oh Sang; Kim, Jeong Han; Lee, Chang Hong; Kwon, So Young

    2011-01-01

    Background/Aims The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea. Methods A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009. Results One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total-bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents. Conclusions The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment. PMID:22310795

  14. Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

    SciTech Connect

    Poggi, Guido, E-mail: guido.poggi@fsm.it [Istituto Scientifico di Pavia, Department of Oncology, IRCCS Fondazione S. Maugeri (Italy); Quaretti, Pietro, E-mail: pquaretti@smatteo.pv.it [IRCCS Policlinico San Matteo, Department of Interventional Radiology (Italy); Montagna, Benedetta, E-mail: b.montagna@fsm.it; Sottotetti, Federico, E-mail: f.sottotetti@fsm.it; Tagliaferri, Barbara, E-mail: b.tagliaferri@fsm.it; Pozzi, Emma, E-mail: v.pozzi@fsm.it; Amatu, Alessio, E-mail: a.amatu@fsm.it; Pagella, Chiara; Bernardo, Giovanni, E-mail: g.bernardo@fsm.it [Istituto Scientifico di Pavia, Department of Oncology, IRCCS Fondazione S. Maugeri (Italy)

    2011-02-15

    Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

  15. 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

  16. Autoimmune reaction to a liver specific membrane antigen during acute viral hepatitis.

    PubMed Central

    Cochrane, A M; Moussouros, A; Smith, A; Thomson, A D; Eddleston, A L; Williams, R

    1976-01-01

    Lymphocyte cytotoxicity for isolated hepatocytes has been demonstrated in 93% of cases of acute viral hepatitis tested within two weeks of the onset of symptoms. The frequency of cytotoxicity during this time was similar for HBsAg positive and negative cases. However, after this time it was significantly higher in HBsAg positive than negative cases, 90% and 25% respectively (P less than 0-01). Cytotoxicity was found in B-cell, but not T-cell, enriched fractions of lymphocytes, compatible with an antibody-dependent K-cell mediated reaction. In two cases the assay remained positive on retesting six months later, and follow-up liver biopsies showed the features of chronic aggressive hepatitis. These findings suggest that, in addition to the known immunological reactions against viral antigens that occur during the acute phase of viral hepatitis, an autoimmune reaction directed against a liver specific protein is also initiated; and if this reaction persists then chronic hepatitis may develop. PMID:61905

  17. Sequential occurrence of acute hepatitis B among members of a high school Sumo wrestling club.

    PubMed

    Bae, Sung Kwan; Yatsuhashi, Hiroshi; Takahara, Ikuko; Tamada, Yoko; Hashimoto, Satoru; Motoyoshi, Yasuhide; Ozawa, Eisuke; Nagaoka, Shinya; Yanagi, Kenji; Abiru, Seigo; Komori, Atsumasa; Ishibashi, Hiromi

    2014-10-01

    A 17-year-old male was admitted to our hospital and diagnosed with acute hepatitis B. Six weeks later, a 15-year-old male was admitted with acute hepatitis B as well. They were Sumo wrestling players in the same club. A detailed survey in the club revealed that a 28-year-old male coach was a hepatitis B surface antigen carrier with high-level viremia. The consistency of hepatitis B virus (HBV) DNA in the infected players was revealed by analyzing the complete HBV genome sequences. Sumo players are more likely to get injured, including cuts and bleeding, compared with players of other sports because of the characteristic wrestling style. Several past reports have suggested that highly viremic HBV carriers have high HBV DNA titers in both their blood and other body fluids such as sweat. In our cases, percutaneous HBV transmission through the bleeding wounds was the most probable infection route. We conclude that a universal HBV immunization program should be introduced urgently in Japan, similar to those implemented in other countries worldwide. PMID:24007264

  18. Comparative Effects of Several Therapatic Agents on Hepatic Damage Induced by Acute Experimental Pancreatitis

    Microsoft Academic Search

    Mukaddes E?refo?lu; Mehmet Gül; Fahri Turan

    2008-01-01

    Purpose The prognosis of acute pancreatitis (AP) depends upon the degree of pancreatic necrosis and the intensity of multisystem\\u000a organ failure. The liver contributes to the systemic manifestations of AP by releasing some cytokines. This study was undertaken\\u000a to examine comparative effects of melatonin, antioxidant mixture containing L(+)-ascorbic acid and N-acetyl cysteine, pentoxifylline and l-arginine on hepatic damage induced by

  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. 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

  1. Acute Hepatic Encephalopathy Presenting as Cortical Laminar Necrosis: Case Report

    PubMed Central

    Choi, Jong Mun; Roh, Sook Young

    2013-01-01

    We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia. PMID:23482893

  2. [Hepatitis E virus: A new entity].

    PubMed

    Selves, Janick; Kamar, Nassim; Mansuy, Jean-Michel; Péron, Jean-Marie

    2010-12-01

    Hepatitis E virus (HEV) is a RNA enterically transmitted virus that causes large waterborne epidemics of acute hepatitis E in endemic regions (Asia and Africa). Sporadic hepatitis E is an emerging disease in developed countries such as France. The majority of acute hepatitis E in France is indigenous (non travel-associated) and is due to infection with HEV genotype 3. Diagnosis is made on the presence of specific serum antibodies and on viral RNA detection in serum or stools. Characteristic pathological signs of acute hepatitis E are severe intralobular necrosis, polymorph inflammation and acute cholangitis in portal tract with numerous neutrophils. Severe forms of hepatitis are associated with underlying chronic liver disease such alcoholic disease. In immunocompetent patients, HEV causes acute resolutive hepatitis and there is no chronic evolution. Conversely, chronic hepatitis E is frequent in immunocompromised patients with a risk of rapid evolution to cirrhosis. Histologic lesions of chronic hepatitis E are similar to those observed in patients chronically infected with hepatitis C virus with dense lymphocytic portal infiltrate, constant peacemeal necrosis and fibrosis. PMID:21167429

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

    PubMed

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

    2014-04-01

    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

  4. 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

  5. [Histomorphometric characteristic of human brain in acute alcoholic intoxication].

    PubMed

    Shormanov, S V; Shormanova, N S

    2005-01-01

    Different brain sections were studied in 20 subjects, who died of ethanol intoxication and in 14 subjects who died of injuries of the heart and main vessels, in order to detect histological changes in the brain and for the purpose of defining spatial and quantitative ratios between cerebral tissue structures in alcoholic intoxication. Different histological, stereometric and morphometric tools were made use of. It was demonstrated that, in alcoholic intoxication, there occur severe disorders of the circulation with affection of vessels in the brain; there are also dystrophic and necrotic changes in neurocytes, glial cells and white substance. The square of neurons shrinks due to death of some of them in the cortex of hemispheres, thalamus and cerebellum. As for the medulla, they are more resistant, there, to ethanol. The diameter of capillaries in the studied brain sections diminishes due to a reduced tonus of cerebral arteries; the quantity of such vessels increases within a standard area, which is conditioned by the compensatory opening of reserve capillaries. All this can be important in dealing with issues of thanatogenesis and of forensic medical diagnosis in death of alcoholic intoxication. PMID:15881135

  6. Lycopodium similiaplex-induced acute hepatitis: a case report.

    PubMed

    Conti, Emma; De Checchi, Giovanna; Mencarelli, Roberto; Pinato, Samuela; Rovere, Pierangelo

    2008-05-01

    A 46-year-old woman was admitted to our department with symptoms of nausea, anorexia and asthenia. Serum alanine aminotransferase and aspartate aminotransferase levels were increased; all serological tests for viral hepatitis and autoimmune disorders were negative. She had taken Lycopodium similiaplex solution as sedative for the previous 8 weeks, whose two constituents, Lycopodium serratum and Chelidonium majus, are found to be potentially toxic. After discontinuing L. similiaplex use, liver values returned to normal and she was asymptomatic. The diagnosis was definitively confirmed by liver biopsy; on the basis of the histological specimen, a hypersensitivity reaction was hypothesized as a possible pathogenic mechanism. Hepatotoxicity of phytotherapy has already been described, although so far, the true incidence and the pathogenic mechanisms are largely unknown. It is important to increase awareness of both clinicians and patients about the potential dangers of herbal remedies; surveillance systems and quality control of these products are necessary. PMID:18403950

  7. Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis.

    PubMed

    McKee, Chad; Sigala, Barbara; Soeda, Junpei; Mouralidarane, Angelina; Morgan, Maelle; Mazzoccoli, Gianluigi; Rappa, Francesca; Cappello, Francesco; Cabibi, Daniela; Pazienza, Valerio; Selden, Claire; Roskams, Tania; Vinciguerra, Manlio; Oben, Jude A

    2015-01-01

    Amphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-? converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also assessed in a mouse model of NASH and in humans with NASH. hHSC time dependently expressed AR and TACE. AR increased hHSC proliferation through several mitogenic signaling pathways such as EGFR, PI3K and p38. AR also induced marked upregulation of hHSC fibrogenic markers and reduced hHSC death. AR expression was enhanced in the HSC of a murine model of NASH and of severe human NASH. In conclusion, AR induces hHSC fibrogenic activity via multiple mitogenic signaling pathways, and is upregulated in murine and human NASH, suggesting that AR antagonists may be clinically useful anti-fibrotics in NAFLD. PMID:25744849

  8. Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis

    PubMed Central

    McKee, Chad; Sigala, Barbara; Soeda, Junpei; Mouralidarane, Angelina; Morgan, Maelle; Mazzoccoli, Gianluigi; Rappa, Francesca; Cappello, Francesco; Cabibi, Daniela; Pazienza, Valerio; Selden, Claire; Roskams, Tania; Vinciguerra, Manlio; Oben, Jude A.

    2015-01-01

    Amphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-? converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also assessed in a mouse model of NASH and in humans with NASH. hHSC time dependently expressed AR and TACE. AR increased hHSC proliferation through several mitogenic signaling pathways such as EGFR, PI3K and p38. AR also induced marked upregulation of hHSC fibrogenic markers and reduced hHSC death. AR expression was enhanced in the HSC of a murine model of NASH and of severe human NASH. In conclusion, AR induces hHSC fibrogenic activity via multiple mitogenic signaling pathways, and is upregulated in murine and human NASH, suggesting that AR antagonists may be clinically useful anti-fibrotics in NAFLD. PMID:25744849

  9. Exercise capacity is not impaired after acute alcohol ingestion: a pilot study.

    PubMed

    Popovic, Dejana; Damjanovic, Svetozar S; Plecas-Solarovic, Bosiljka; Peši?, 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?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

  10. 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

  11. Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL1) and purified human IL1

    Microsoft Academic Search

    G. Ramadori; J. D. SIPE; C. A. DINARELLO; S. B. MIZEL; H. R. COLTEN

    1985-01-01

    The acute phase response is a systemic reaction to inflammation or tissue injury. It is characterized by complex changes that include fever, leukocytosis, increased muscle proteolysis, altered carbohydrate and trace metal metabolism, and a pronounced change in hepatic protein synthesis (1). Within several hours of an acute phase stimulus, the plasma concentrations of C-reactive protein and serum amyloid A (SAA)

  12. Initial sensitivity, acute tolerance and alcohol consumption in four inbred strains of rats

    SciTech Connect

    Khanna, J.M.; Kalant, H.; Sharma, H.; Le, A.D. (Univ. of Toronto, Ontario (Canada))

    1989-02-09

    Initial sensitivity to ethanol (2g/kg, i.p.) was determined in a jumping test in separated groups of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats as well as in Dahl salt-sensitive (SS) and Dahl salt-resistant (SR) rats. Acute tolerance was studied in the same strains, by measuring the response to a second dose (0.7 g/kg) as soon as they had recovered from the first. One week later, voluntary consumption of ethanol was studied in all groups. SH rats were found to be more sensitive than WKY, but there was no difference in acute tolerance development between these two strains. SH rats, however, drank significantly more alcohol than the WKY in both the two-bottle choice paradigm and the limited access model. Similarly, SS rats drank significantly more alcohol than the SR rats, although SS rats were found to be more sensitive to ethanol than SR. There was again no difference in acute tolerance development between these two strains. These observations suggest that difference in alcohol consumption in these strains cannot be accounted for by significant differences in acute tolerance or in initial sensitivity to ethanol.

  13. Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

    PubMed

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

    2014-09-01

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

  14. Why can't Chinese Han drink alcohol? Hepatitis B virus infection and the evolution of acetaldehyde dehydrogenase deficiency.

    PubMed

    Lin, Y-P; Cheng, T-J

    2002-08-01

    An aldehyde-dehydrogenase (ALDH2) deficiency is a biological curb on excess alcohol-drinking. This enzyme deficiency is very common amongst Oriental people while it is relatively rare for most other populations. We observe that there is good geographical correlation between the prevalence of the mutant ALDH2*2 alleles and hepatitis B virus (HBV) infections. Populations that demonstrate a high ALDH2*2 prevalence are all located in HBV-endemic areas. Further, studies have shown that HBV and alcohol drinking exhibit a synergistic effect upon liver cirrhosis and cancer. A shorter life span for those with HBV infection and heavy alcohol consumption may result in a selection of the ALDH2*2 gene. We postulate that there may be patterns of evolutionary adaptation for ALDH2 deficiency in certain HBV-endemic areas and that these adaptations can produce differences in human alcohol-drinking capability. PMID:12208210

  15. Maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia: a meta-analysis

    Microsoft Academic Search

    Xiaoling Zhang; Yaodong Zhang; Qun Hu

    2010-01-01

    Objective  The authors used a meta-analytic technique to quantify the evidence of an association between maternal alcohol consumption\\u000a during pregnancy and childhood acute leukemia (AL), which provided a basis for the prevention of childhood AL.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened. Subgroup\\u000a meta-analysis was conducted according to the type of leukemia. Results of research

  16. Urinary ascites after an alcohol binge: An uncommon treatable cause of acute kidney injury

    PubMed Central

    Jairam, A.; Kachhela, R.; Mukherjee, D.; Hooda, A. K.

    2014-01-01

    A 38-year-old male presented after a binge of alcohol with acute onset, rapidly progressive distension of abdomen, hematuria, oligoanuria and dialysis dependent renal failure. Evaluation revealed ascitic fluid with high creatinine and computed tomography cystogram showed contrast leak into the peritoneum. Retrograde cystoscopy confirmed rupture of the bladder. He had prompt diuresis after indwelling Foley's catheter was placed. By 2 weeks, he had recovered renal function completely. A high index of suspicion can make an early diagnosis and avoid unnecessary investigations. The mechanism of spontaneous rupture of bladder after an alcohol binge is discussed. PMID:25097342

  17. Influence of acute alcohol ingestion on sympathetic neural responses to orthostatic stress in humans.

    PubMed

    Carter, Jason R; Stream, Sarah F; Durocher, John J; Larson, Robert A

    2011-05-01

    Acute alcohol consumption is reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the effects of alcohol on MSNA responses during orthostatic stress have not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects (age 24 ± 1 yr). After an initial progressive LBNP (pretreatment), subjects consumed either alcohol (0.8 g ethanol/kg body mass; n = 15) or placebo (n = 15), and progressive LBNP was repeated (posttreatment). Alcohol increased resting HR (59 ± 2 to 65 ± 2 beats/min, P < 0.05), MSNA (13 ± 3 to 19 ± 4 bursts/min, P < 0.05), and MSNA burst latency (1,313 ± 16 to 1,350 ± 17 ms, P < 0.05) compared with placebo (group × treatment interactions, P < 0.05). During progressive LBNP, a pronounced decrease in MAP was observed after alcohol but not placebo (group × time × treatment, P < 0.05). In contrast, MSNA and HR increased during all LBNP protocols, but there were no differences between trials or groups. However, alcohol altered MSNA burst latency response to progressive LBNP. In conclusion, the lack of MSNA adjustment to a larger drop in arterial blood pressure during progressive LBNP, coupled with altered sympathetic burst latency responses, suggests that alcohol blunts MSNA responses to orthostatic stress. PMID:21325108

  18. Quality of life after liver transplantation for acute hepatic failure.

    PubMed

    Perkins, James D

    2007-11-01

    Liver transplantation is now an accepted and successful therapy for both acute and cronic liver diseases. Whilst the study of health related quality of life (HRQoL) post-transplantation for chronic liver disease (CLD) has been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF), despite super urgent transplantation constituting 16.6% of al United Kingdom liver transplantation. Therefore, the aim of the present study was to document the HRQoL in patients who have received an emergency liver transplant for ALF. Data collection employed between method triangulation, using the Short Form 36 quality of life health questionnaire for both ALF (n=47) and CLD (n=49), and six semi-structured interviews. Only the qualitative element of the study is reported here. Phenomenological analysis of the semi-structured interviews identified four themes relating to the physical changes encountered (inactivity), physical recovery (health transition); changes made to the transplant recipients life styles (modification); and outlook. The majority of transplanted ALF transplant recipients' stated that they have a good quality of life, which was often comparable to their pretransplantation lifestyle. However, the initial recovery process was often difficult and was related to the physical changes instigated from their multi-organ failure and intensive care stay, which can present numerous physical and emotional challenges. PMID:18074431

  19. Detecting impairment: Sensitive cognitive measures of dose-related acute alcohol intoxication.

    PubMed

    Cash, Catherine; Peacock, Amy; Barrington, Helen; Sinnett, Nicholas; Bruno, Raimondo

    2015-04-01

    The cognitive impairment that results from acute alcohol intoxication is associated with considerable safety risks. Other psychoactive substances, such as medications, pose a similar risk to road and workplace safety. However, there is currently no legal limit for operating vehicles or working while experiencing drug-related impairment. The current study sought to identify a brief cognitive task sensitive to a meaningful degree of impairment from acute alcohol intoxication to potentially stand as a reference from which to quantify impairment from other similar substances. A placebo-controlled single-blind crossover design was employed to determine the relative sensitivity of four commonly-administered cognitive tasks (Compensatory Tracking Task, Digit Symbol Substitution Test, Brief Stop Signal Task and Inspection Time Task) to alcohol-related impairment in male social drinkers at ~0.05% ascending breath alcohol concentration (BrAC), ~0.08% peak BrAC and 0.05% descending BrAC. The Inspection Time Task was identified as the most sensitive task, detecting a medium to large magnitude increase in impairment (g ? 0.60) at 0.05% ascending and descending BrAC, and a large magnitude effect size (g = 0.80) at 0.08% peak BrAC. The remaining tasks failed to demonstrate sensitivity to dose-dependent and limb-dependent changes in alcohol-induced impairment. The Inspection Time Task was deemed the most sensitive task for screening alcohol-related impairment based on the present results. Confirmation of equivalence with other drug-related impairment and sensitivity to alcohol-induced impairment in real-world settings should be established in future research. PMID:25691502

  20. Prognostic value of gallbladder wall thickening in patients with acute hepatitis A

    PubMed Central

    2015-01-01

    Purpose: To investigate the clinical significance of gallbladder (GB) wall thickening frequently observed in patients with acute hepatitis A. Methods: A total of 328 consecutive patients who were diagnosed with acute hepatitis A and underwent abdominal ultrasonography were enrolled retrospectively. Patients were divided into two groups: GB wall thickening (?3 mm, group A) and no thickening (group B). Group A was subdivided into two subgroups (GB wall thickening of ?10 mm, group A-1 and ?3 mm to <10 mm, group A-2). The laboratory results related to liver function, hospitalization duration, and time to normalization of liver function were compared between the groups. Results: A total of 230 patients showed GB wall thickening (group A). Besides gamma-glutamyl transpeptidase and alkaline phosphatase, all laboratory results of group A were significantly higher than those of group B (P<0.05). Compared with group B, the hospitalization duration and the time to normalization of liver function were significantly longer in group A (P<0.05). Group A-1 included 146 patients and group A-2 included 84 patients. No significant differences in laboratory results, hospitalization duration, and time to normalization of liver function were found between the two subgroups. In the multivariate logistic regression analysis, serum alanine transaminase, total bilirubin and albumin levels, and hospitalization duration were significantly associated with GB wall thickening in patients with hepatitis A. Conclusion: The presence of GB wall thickening in patients with acute hepatitis A suggests a poorer prognosis irrespective of the degree of GB wall thickening or the degree of liver enzyme elevation. PMID:25672770

  1. 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

  2. Alcohol

    MedlinePLUS

    ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart disease, ... work, and with friends. NIH: National Institute on Alcohol Abuse and Alcoholism

  3. 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

  4. [Acute hepatitis due to infectious mononucleosis in a 21-year-old-man].

    PubMed

    Modesto Dos Santos, Vitorino; Da Costa Arruda, Zilcem; De Farias Polcheira, Maira; Da Silva De Souza, Diogo Wagner; Rodrigues Oliveira Santos, Alessandra Maria; Santos Corrêa Da Costa, Marcela

    2013-07-01

    A 21-year-old mole was admitted because of fever, fatigue, headache, pharyngitis, abdominal pain, loss of appetite, vomiting and dark urine for three days. The patient denied recent use of medicines or any other drug. His physical examination disclosed jaundice, hepato-splenomegaly, whitish-yellow covered tonsils, bilateral anterior and posterior cervical lymph node enlargement associated with edema on the face and neck. Routine blood tests detected abnormalities in serum bilirubins and liver enzymes (total bilirubin: 14.5 mg/dl, direct-reacting bilirubin: 12.9 mg/dl, AST: 697 U/l, ALT: 619 U/l, alkaline phosphatases: 260 U/l, and GGT: 413 U/l). Serological tests showed negative results for viral hepatitis, cytomegalovirus, HIV-1 and HIV-2, and toxoplasmosis markers, while serology for recent infection by EBV was positive (IgM: 70 and 29 U/ml; EBV IgG: 25 and 156 U/ml). Although infrequently, EBV infection can cause acute hepatitis with accentuated cholestatic jaundice (5% of cases), which may constitute an additional diagnostic challenge for primary care physicians. The patient improved with supportive management and was discharged after 12 days. This case study might contribute to increase the suspicion index about acute hepatitis related to EBV. PMID:24356741

  5. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study

    Microsoft Academic Search

    Aezam Katoonizadeh; Wim Laleman; Chris Verslype; Alexander Wilmer; Geert Maleux; Tania Roskams; Frederik Nevens

    2010-01-01

    Background‘Acute-on-chronic liver failure’ (ACLF) is characterised in a more advanced stage by liver failure associated with multiple other end-organ failure. The global clinical characteristics of this entity remain, however, ill-defined.ObjectiveTo characterise and evaluate the clinicopathological features of patients with ACLF compared with patients with chronic decompensated cirrhosis (CHD) in a prospective, homogeneous cohort of patients with histologically proven alcoholic cirrhosis

  6. Enhanced urinary excretion of cysteinyl leukotrienes in patients with acute alcohol intoxication

    Microsoft Academic Search

    Masahito Uemura; Wolf-dieter Lehmann; Winfried Schneider; Helmut K. Seitz; Axel Benner; Andrea Keppler-Hafkemeyer; Peter Hafkemeyer; Hideyuki Kojima; Masao Fujimoto; Tadasu Tsujii; Hiroshi Fukui; Dietrich Keppler

    2000-01-01

    Background & Aims: Leukotrienes are proinflammatory mediators. Ethanol inhibits the catabolism of both cysteinyl leukotrienes (leukotriene E4 [LTE4] and N-acetyl-LTE4) and leukotriene B4 (LTB4) in hepatocytes. We examined the metabolic derangement of leukotriene inactivation by ethanol in humans in vivo. Methods: LTE4, N-acetyl-LTE4, LTB4, and 20-hydroxy-LTB4 were quantified in urine samples from 16 patients with acute alcohol intoxication (mean blood

  7. Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice

    PubMed Central

    Yu, Shuna; Zheng, Jie; Jiang, Zhengchen; Shi, Caixing; Li, Jin; Du, Xiaodong; Wang, Hailiang; Jiang, Jiying; Wang, Xin

    2013-01-01

    The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury. PMID:23994834

  8. Alcohol-impaired speed and accuracy of cognitive functions: a review of acute tolerance and recovery of cognitive performance.

    PubMed

    Schweizer, Tom A; Vogel-Sprott, Muriel

    2008-06-01

    Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews the results of recent research using these tasks to test the development of acute tolerance in cognitive performance and recovery from impairment during declining BACs. Results show that speed and accuracy do not necessarily agree in detecting cognitive impairment, and this mismatch most frequently occurs during declining BACs. Speed of cognitive performance usually recovers from impairment to drug-free levels during declining BACs, whereas alcohol-increased errors fail to diminish. As a consequence, speed of cognitive processing tends to develop acute tolerance, but no such tendency is shown in accuracy. This "acute protracted error" phenomenon has not previously been documented. The findings pose a challenge to the theory of alcohol tolerance on the basis of physiological adaptation and raise new research questions concerning the independence of speed and accuracy of cognitive processes, as well as hemispheric lateralization of alcohol effects. The occurrence of alcohol-induced protracted cognitive errors long after speed returned to normal is identified as a potential threat to the safety of social drinkers that requires urgent investigation. PMID:18540784

  9. Dose-Reduced Trastuzumab Emtansine: Active and Safe in Acute Hepatic Dysfunction

    PubMed Central

    Sharp, Adam; Johnston, Stephen R.D.

    2015-01-01

    Breast cancer is the most common cancer in women worldwide. The majority of deaths attributed to breast cancer are a result of metastatic disease, and 30% of early breast cancers (EBC) will develop distant disease. The 5-year survival of patients with metastatic disease is estimated at 23%. Breast cancer subtypes continue to be stratified histologically on oestrogen, progesterone and human epidermal growth factor-2 (HER2) receptor expression. HER2-positive breast cancers represent 25% of all breast cancer diagnoses. The therapies available for metastatic breast cancer (MBC) are expanding, in particular within the field of HER2-positive disease, with the approval of trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (TDM-1). Recently, TDM-1 has been shown to improve progression-free survival in HER2 MBC when compared to capecitabine and lapatinib in clinical studies. Its main toxicities are deranged liver function tests and thrombocytopenia. There have also been cases of acute liver failure. Therefore, its use in acute hepatic dysfunction, to our knowledge, has been neither studied nor reported. We report a patient with progressive HER2-positive MBC who had previously responded to multiple HER2-targeted therapies that presented with acute hepatic dysfunction. She was treated with dose-reduced TDM-1 safely, with clear evidence of rapid biochemical, clinical and radiological response. This allowed dose escalation of TDM-1, and the patient maintains an ongoing response. PMID:25873876

  10. Acute hepatitis: a rare complication of Epstein-Barr virus (EBV) infection.

    PubMed

    Ulu?, Mehmet; Celen, Mustafa Kemal; Ayaz, Celal; Geyik, Mehmet Faruk; Ho?o?lu, Salih

    2010-10-01

    Infectious Mononucleosis (IM), a benign lymphoproliferative disease, is the best known clinical syndrome caused by Epstein-Barr Virus (EBV). It usually resolves over a period of weeks or months without sequelae but may occasionally be complicated by a wide variety of neurologic, hematologic, hepatic, respiratory, and psychological complications. In this report we describe a patient with acute hepatitis following EBV-IM in a previously healthy woman. A 26-year-old woman who presented with fever, generalized weakness, nausea, sore throat, yellowing of skin, and a generalized skin rash was admitted to our clinic. Tonsillar enlargement, pharyngeal erythema, palatal petechiae, lymphadenopathy, and jaundice were noted. Significant atypical lymphocytes ( > 10%) were seen on the peripheral blood smear. Liver function tests such as ALT: 303 U/L, AST: 172 U/L, ALP: 193 U/L and total bilirubin: 7.3 mg/dl were elevated. Serological tests for EBV infection were consistent with acute infection (EBV virus capsid antigen was reactive with IgM and IgG antibodies). The Monospot test was also positive. On the seventh day, liver function tests and bilirubin had risen to peak level and platelets were decreased. The patient was managed supportively and her critical condition improved and was finally stabilized. Although the prognosis for IM is very favorable, a variety of acute complications may occur. PMID:21045362

  11. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

    PubMed Central

    Gillis, J. H.; Satapathy, S. K.; Parsa, L.; Sylvestre, P. B.; Dbouk, N.

    2015-01-01

    Acute sickle hepatic crisis (ASHC) has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS) sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  12. 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

  13. The inflammasome in alcoholic hepatitis: Its relationship with Mallory-Denk body formation.

    PubMed

    Peng, Yue; French, Barbara A; Tillman, Brittany; Morgan, Timothy R; French, Samuel W

    2014-10-01

    Recent studies indicate that the inflammasome activation plays important roles in the pathogenesis of alcoholic hepatitis (AH). Nod-like receptor protein 3 (NLRP3) is a key component of the macromolecular complex that is so called the inflammasome that triggers caspase 1-dependent maturation of the precursors of IL-1? 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-1?, IL-18, and other inflammatory components including IL-6, IL-10, TNF-?, IFN-?, STAT3, and 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, and TNF-? 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 and 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

  14. Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis.

    PubMed

    Foureau, D M; Walling, T L; Maddukuri, V; Anderson, W; Culbreath, K; Kleiner, D E; Ahrens, W A; Jacobs, C; Watkins, P B; Fontana, R J; Chalasani, N; Talwalkar, J; Lee, W M; Stolz, A; Serrano, J; Bonkovsky, H L

    2015-04-01

    Drug-induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n?=?32) versus non-DILI causes of acute liver injury (n?=?25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 [T cytotoxic and natural killer (NK) cells] were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8(+) T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD. PMID:25418487

  15. Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis

    PubMed Central

    Takahashi, Hideaki; Shigefuku, Ryuta; Yoshida, Yoshihito; Ikeda, Hiroki; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2014-01-01

    AIM: To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC). METHODS: The subjects included 35 patients with AL-LC (34 men, 1 woman; mean age, 58.9 ± 10.7 years; median age, 61 years; range: 37-76 years). All patients were enrolled in this study after obtaining written informed consent. Liver function was measured with tests measuring albumin (Alb), prothrombin time (PT), brain natriuretic peptide (BNP), branched amino acid and tyrosine ratio (BTR), branched chain amino acid (BCAA), tyrosine, ammonia (NH3), cholinesterase (ChE), immunoreactive insulin (IRI), total bile acid (TBA), and the retention rate of indocyanine green 15 min after administration (ICG R15). Hepatic blood flow, hepatic arterial tissue blood flow (HATBF), portal venous tissue blood flow (PVTBF), and total hepatic tissue blood flow (THTBF) were simultaneously calculated using xenon computed tomography. RESULTS: PVTBF, HATBF and THTBF were 30.2 ± 10.4, 20.0 ± 10.7, and 50.3 ± 14.9 mL/100 mL/min, respectively. Alb, PT, BNP, BTR, BCAA, tyrosine, NH3, ChE, IRI, TBA, and ICG R15 were 3.50 ± 0.50 g/dL, 72.0% ± 11.5%, 63.2 ± 56.7 pg/mL, 4.06 ± 1.24, 437.5 ± 89.4 ?mol/L, 117.7 ± 32.8 ?mol/L, 59.4 ± 22.7 ?g/dL, 161.0 ± 70.8 IU/L, 12.8 ± 5.0 ?g/dL, 68.0 ± 51.8 ?mol/L, and 28.6% ± 13.5%, respectively. PVTBF showed a significant negative correlation with ICG R15 (r = -0.468, P <0.01). No significant correlation was seen between ICG 15R, HATBF and THTBF. There was a significant correlation between PVTBF and Alb (r = 0.2499, P < 0.05), and NH3 tended to have an inverse correlation with PVTBF (r = -0.2428, P = 0.0894). There were also many significant correlations between ICG R15 and liver function parameters, including Alb, NH3, PT, BNP, TBA, BCAA, and tyrosine (r = -0.2156, P < 0.05; r = 0.4318, P < 0.01; r = 0.4140, P < 0.01; r = 0.3610, P < 0.05; r = 0.5085, P < 0.001; r = 0.4496, P < 0.01; and r = 0.4740, P < 0.05, respectively). CONCLUSION: Our investigation showed that there is a close correlation between liver function and hepatic blood flow. PMID:25493018

  16. RIFLE criteria and hepatic function in the assessment of acute renal failure in liver transplantation.

    PubMed

    Tinti, F; Umbro, I; Meçule, A; Rossi, M; Merli, M; Nofroni, I; Corradini, S Ginanni; Poli, L; Pugliese, F; Ruberto, F; Berloco, P B; Mitterhofer, A P

    2010-05-01

    Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney. PMID:20534269

  17. 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

  18. [Purtscher's retinopathy: a rare complication of acute non-alcoholic pancreatitis].

    PubMed

    Núñez, L; Cubiella, J; Moreno, C; Díez, M S; Sánchez, E; Vega, M

    2003-11-01

    Purtscher's retinopathy is a rare complication of acute alcoholic pancreatitis that is characterized by the development of cotton-wool exudates and retinal hemorrhages located around the optic disk. Its development is due to ischemic phenomena in the posterior pole of the retina due to microemboli in the retinal arterioles and capillaries. This complication is not related to a poorer prognosis of acute pancreatitis and the retinopathy usually has a favorable outcome with disappearance of the ophthalmic lesions and restoration of visual acuity after 4-6 weeks in most cases. However, some patients may show residual lesions, especially if optical atrophy occurs. We present a 40-year-old woman with loss of visual acuity due to Purtscher's retinopathy during the course of mild acute idiopathic pancreatitis. PMID:14642240

  19. Assessment of the Model for End-stage Liver Disease (MELD) Score in Predicting Prognosis of Patients with Alcoholic Hepatitis

    PubMed Central

    Goyal, Sundeep K.; Dixit, Vinod K.; Jain, Ashok K.; Mohapatra, Pradeep K.; Ghosh, Jayant K.

    2014-01-01

    Background Traditionally, Maddrey discriminant function (DF) score has been used for stratifying the prognosis of alcoholic hepatitis. Recently, the Model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator. Another new prognostic approach, Lille model has been also suggested to accurately identify patients at high risk of death. Therefore, this prospective study was aimed to compare MELD, DF, Child–Turcotte–Pugh (CTP) scores and Lille model for predicting the short-term mortality in Indian patients with alcoholic hepatitis. Methods We calculated the DF, CTP, MELD and Lille scores in patients hospitalized with alcoholic hepatitis & evaluated if the scores predicted in-hospital mortality. Results A total of 104 patients were enrolled and thirty-two (30.7%) patients died during the hospitalization (2–30 days). Admission DF score (OR 1.1, P < 0.04), CTP (OR 2, P < 0.05) MELD score (OR 2.2, P < 0.005) and first week MELD score (OR 1.1, P < 0.05) were independently associated with in-hospital mortality. The area under the receiver-operating curve (AUROC) for the admission and day 7 MELD score was significantly higher than CTP score and was comparable to DF score and Lille model (AUC & 95% CI: 0.97 [0.95–1.0], 0.99 [0.99–1.0], 0.91 [0.83–0.91] and 0.92 [0.86–0.98] for MELD at admission & day 7, admission DF and Lille model, respectively). The MELD score >14 at admission and >12 at day 7 had high sensitivity and specificity in predicting short-term mortality (96%, 89% and 95%, 98% respectively). The cutoff of 0.45 for the Lille model was able to identify 79% of the observed deaths, whereas DF score ?32 for DF were able to identify 85%. Conclusion MELD score, as a predictive model for assessment of short-term mortality in alcoholic hepatitis is better than CTP and comparable to DF and Lille model. PMID:25755531

  20. Hepatic venous pressure gradient measurement before TIPS for acute variceal bleeding

    PubMed Central

    Qi, Xing-Shun; Fan, Dai-Ming

    2014-01-01

    Hepatic venous pressure gradient (HVPG) is an independent predictor of variceal rebleeding in patients with cirrhosis. After pharmacological and/or endoscopic therapy, the use of a transjugular intrahepatic portosystemic shunt (TIPS) may be necessary in HVPG non-responders, but not in responders. Thus, HVPG measurement may be incorporated into the treatment algorithm for acute variceal bleeding, which further identifies the candidates that should undergo early insertion of TIPS or maintain the traditional pharmacological and/or endoscopic therapy. The potential benefits are to reduce the cost and prevent TIPS-related complications. PMID:24966625

  1. Hepatic venous pressure gradient measurement before TIPS for acute variceal bleeding.

    PubMed

    Qi, Xing-Shun; Fan, Dai-Ming

    2014-06-21

    Hepatic venous pressure gradient (HVPG) is an independent predictor of variceal rebleeding in patients with cirrhosis. After pharmacological and/or endoscopic therapy, the use of a transjugular intrahepatic portosystemic shunt (TIPS) may be necessary in HVPG non-responders, but not in responders. Thus, HVPG measurement may be incorporated into the treatment algorithm for acute variceal bleeding, which further identifies the candidates that should undergo early insertion of TIPS or maintain the traditional pharmacological and/or endoscopic therapy. The potential benefits are to reduce the cost and prevent TIPS-related complications. PMID:24966625

  2. [Efficiency of groprinosine in the complex treatment of acute virus hepatitis B].

    PubMed

    Karimov, I Z

    2004-01-01

    35 patients with acute virus hepatitis of average severity were examined. They developed after short-term improvement of general state a negative dynamics of clinical and laboratory indexes. 21 patients have received traditional treatment, 14 patients additionally were prescribed groprinosine in a dose of 50 mg/kg daily per/os within 5-10 days. It was shown, that addition of gropfmosme to complex therapy positively influenced on the disease's course, promoted a rapid regress of clinical symptoms, normalization of biochemical indexes of liver's functions and decreased days of hospitalization. PMID:15724621

  3. 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.

  4. Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis

    PubMed Central

    Lee, Minjong; Kim, Won; Choi, Yunhee; Kim, Sunhee; Kim, Donghee; Yu, Su Jong; Lee, Jeong-Hoon; Kim, Hwi Young; Jung, Yong Jin; Kim, Byeong Gwan; Kim, Yoon Jun; Yoon, Jung-Hwan; Lee, Kook Lae; Lee, Hyo-Suk

    2014-01-01

    The accurate prognostic stratification of alcoholic hepatitis (AH) is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort) and 106 patients with AH between 2005 and 2012 (a validation cohort). The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL) were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC). For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001). In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment. PMID:25013906

  5. 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

  6. 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

  7. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease

    PubMed Central

    Liu, Yang-Lin; Reeves, Helen L.; Burt, Alastair D.; Tiniakos, Dina; McPherson, Stuart; Leathart, Julian B. S.; Allison, Michael E. D.; Alexander, Graeme J.; Piguet, Anne-Christine; Anty, Rodolphe; Donaldson, Peter; Aithal, Guruprasad P.; Francque, Sven; Van Gaal, Luc; Clement, Karine; Ratziu, Vlad; Dufour, Jean-Francois; Day, Christopher P.; Daly, Ann K.; Anstee, Quentin M.

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD. PMID:24978903

  8. Nephronectin is upregulated in acute and chronic hepatitis and aggravates liver injury by recruiting CD4 positive cells.

    PubMed

    Inagaki, Fuyuki F; Tanaka, Minoru; Inagaki, Natsuko F; Yagai, Tomoki; Sato, Yuya; Sekiguchi, Kiyotoshi; Oyaizu, Naoki; Kokudo, Norihiro; Miyajima, Atsushi

    2013-01-11

    Nephronectin (Npnt) is an extracellular matrix protein known to play a critical role in kidney development; however, its physiological role in the liver remains elusive. Here we show that Npnt expression is upregulated in mouse models of both acute and chronic hepatitis induced by Concanavalin A (Con A) and 3,5-diethocarbonyl-1,4-dihydrocollidine (DDC), respectively. In both models, Npnt was localized in inflammatory foci and was mainly secreted from mesenchymal cells and in part by cholangiocytes. Interestingly, ectopic expression of Npnt in hepatocytes induced the development of granuloma-like cell clusters mainly composed of CD4(+) T cells or NKT cells but did not induce apparent hepatitis. Furthermore, we found that Npnt exacerbated the Con A-induced acute hepatitis. These results indicate that Npnt plays an important role in the initiation of hepatitis by recruiting CD4(+) T cells or NKT cells into the foci of inflammation. In addition, we reveal that Npnt expression is also upregulated in human hepatitis. Therefore, Npnt may be a potential therapeutic target for acute and chronic hepatitis. PMID:23206711

  9. Alcoholic liver disease

    MedlinePLUS

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Alcohol can cause inflammation in the liver . Over time, scarring ...

  10. 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

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

    SciTech Connect

    Radeleff, Boris, E-mail: Boris_Radeleff@med.uni-heidelberg.de; Sommer, Christof-Matthias; Heye, Tobias; Lopez-Benitez, Ruben [University of Heidelberg Medical Center, Department of Diagnostic Radiology (Germany); Sauer, Peter [University of Heidelberg Medical Center, Department of Internal Medicine IV, Gastroenterology, Hepatology, Infectious Diseases, and Intoxications (Germany); Schmidt, Jan [University of Heidelberg Medical Center, General, Visceral, and Accident Surgery (Germany); Kauczor, Haus-Ulrich; Richter, Goetz Martin [University of Heidelberg Medical Center, Department of Diagnostic Radiology (Germany)

    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.

  12. Please cite this article in press as: X. Chen, et al. Dynamics of acute hepatitis B virus infection in chimpanzees, Math. Comput. Simul. (2013), http://dx.doi.org/10.1016/j.matcom.2013.05.003

    E-print Network

    Kuang, Yang

    Please cite this article in press as: X. Chen, et al. Dynamics of acute hepatitis B virus infection in Simulation xxx (2013) xxx­xxx Original article Dynamics of acute hepatitis B virus infection in chimpanzees a minimum virus infection model aiming at explaining why two acute hepatitis B virus (HBV) infected

  13. 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

  14. 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

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

    PubMed

    Paw?owska, Ma?gorzata; Halota, Waldemar

    2010-10-27

    A 16 year-old girl was admitted to hospital because of fatigue and somnolence, nausea, epistaxis and jaundice. Physical examination revealed jaundice, an enlarged liver and tenderness of upper right abdomen. Laboratory tests revealed an increased level of acute liver failure, bilirubin, bile acids, GGTP and a decreased prothrombin ratio, with elevated gamma-globulin and IgG levels, and the presence of anti-mitochondrial M2 antibodies and HBV infection markers. The patient was diagnosed with liver failure resulting from chronic hepatitis B with an autoimmune component. The treatment consisted of steroids, azathioprine, vitamin K, low-protein diet and lactulose enemas. After undergoing a molecular test (HBV DNA 3.23 × 10(5) IU/mL and mutations I 204 and I 80), the treatment was modified by adding entecavir. After one month the patient was discharged in good clinical condition, with the recommendation of continued entecavir, prednisone and azathioprine. In subsequent months, no clinical deterioration or abnormal biochemical liver function test results were found, despite the discontinuation of immunosuppressive therapy after 10 mo. The patient continues entecavir therapy. PMID:21160949

  16. 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 ?-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

  17. 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

  18. Hepatitis C: Treatment

    MedlinePLUS

    ... C virus ribonucleic acid level or hepatitis C RNA level) This test measures the amount of hepatitis ... in Drug/Alcohol Recovery Alcoholics Anonymous A.A. World Services, Inc. P.O. Box 459 New York, ...

  19. Rapid spontaneous resolution of acute subdural haematoma in a patient with chronic alcoholism.

    PubMed

    Hadjigeorgiou, Georgios; Chamilos, Christos; Petsanas, Adamantios; Vranos, Georgios; Foteas, Pavlos; Spiridakis, Filokypros

    2012-06-01

    Acute subdural haematoma (ASDH) constitutes one of the most critical emergencies in neurosurgery. There are only several reports that show the rapid disappearance of ASDH without surgical intervention. We report a case of a 64-year-old alcoholic man who had a traumatic subdural haematoma after a fall from a height of about eight meters on level ground. The computed tomography (CT) of the brain on admission demonstrated a left parietooccipital ASDH. A follow-up CT scan after 8 hours showed resolution of the hematoma. The patient was discharged 9 days later with no neurological deficit. We discuss the possible mechanisms of the rapid resolution of the ASDH. PMID:22111954

  20. Octacosanol Attenuates Disrupted Hepatic Reactive Oxygen Species Metabolism Associated with Acute Liver Injury Progression in Rats Intoxicated with Carbon Tetrachloride

    PubMed Central

    Ohta, Yoshiji; Ohashi, Koji; Matsura, Tatsuya; Tokunaga, Kenji; Kitagawa, Akira; Yamada, Kazuo

    2008-01-01

    We examined whether octacosanol, the main component of policosanol, attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride (CCl4). In rats intoxicated with CCl4 (1 ml/kg, i.p.), the activities of serum transaminases increased 6 h after intoxication and further increased at 24 h. In the liver of CCl4-intoxicated rats, increases in lipid peroxide (LPO) concentration and myeloperoxidase activity and decreases in superoxixde dismutase activity and reduced glutathione (GSH) concentration occurred 6 h after intoxication and these changes were enhanced with an increase in xanthine oxidase activity and a decrease in catalase activity at 24 h. Octacosanol (10, 50 or 100 mg/kg) administered orally to CCl4-intoxicated rats at 6 h after intoxication attenuated the increased activities of serum transaminases and the increased hepatic myeloperoxidase and xanthine oxidase activities and LPO concentration and the decreased hepatic superoxide dismutase and catalase activities and GSH concentration found at 24 h after intoxication dose-dependently. Octacosanol (50 or 100 mg/kg) administered to untreated rats decreased the hepatic LPO concentration and increased the hepatic GSH concentration. These results indicate that octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in CCl4-intoxicated rats. PMID:18385828

  1. 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

  2. Nine scoring models for short-term mortality in alcoholic hepatitis: cross-validation in a biopsy-proven cohort

    PubMed Central

    Papastergiou, V; Tsochatzis, E A; Pieri, G; Thalassinos, E; Dhar, A; Bruno, S; Karatapanis, S; Luong, T V; O'Beirne, J; Patch, D; Thorburn, D; Burroughs, A K

    2014-01-01

    Background Several prognostic models have emerged in alcoholic hepatitis (AH), but lack of external validation precludes their universal use. Aim To validate the Maddrey Discriminant Function (DF); Glasgow Alcoholic Hepatitis Score (GAHS); Mayo End-stage Liver Disease (MELD); Age, Bilirubin, INR, Creatinine (ABIC); MELD-Na, UK End-stage Liver Disease (UKELD), and three scores of corticosteroid response at 1 week: an Early Change in Bilirubin Levels (ECBL), a 25% fall in bilirubin, and the Lille score. Methods Seventy-one consecutive patients with biopsy-proven AH, admitted between November 2007-September 2011, were evaluated. The clinical and biochemical parameters were analysed to assess prognostic models with respect to 30- and 90-day mortality. Results There were no significant differences in the areas under the receiver operating characteristics curve (AUROCs) relative to 30-day/90-day mortality: MELD 0.79/0.84, DF 0.71/0.74, GAHS 0.75/0.78, ABIC 0.71/0.78, MELD-Na 0.68/0.76, UKELD 0.56/0.68. One-week rescoring yielded a trend towards improved predictive accuracies (30-day/90-day AUROCs: 0.69–0.84/0.77–0.86). In patients with admission DF ?32 (n = 31), response to corticosteroids according to ECBL, 25% fall in bilirubin and the Lille model yielded AUROCs of 0.73/0.73, 0.78/0.72 and 0.81/0.82 for a 30-day/90-day outcome respectively. All models showed excellent negative predictive values (NPVs; range: 86–100%), while the positive ones were low (range: 17–50%). Conclusions MELD, DF, GAHS, ABIC and scores of corticosteroid response proved to be valid in an independent cohort of biopsy-proven alcoholic hepatitis. MELD modifications incorporating sodium did not confer any prognostic advantage over classical MELD. Based on excellent NPVs, the models are best to identify patients at low risk of death. PMID:24612165

  3. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

    PubMed Central

    Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P.J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a high-fat diet (SFL model) or a methionine-choline-deficient diet (NASH model) for eight weeks. Hepatic uptake transporter function was determined by bromosulfophthalein (BSP) disposition. Transporter expression was determined by branched DNA signal amplification assay and western blotting; inflammation was identified by immunostaining of liver slices for interleukin 1 beta (IL-1?). MC- rats showed significant retention of BSP in the plasma when compared to control rats. Hepatic NTCP, OATP1a1, 1a4, 1b2 and 2b1; and OAT 2 and 3 mRNA levels were significantly decreased in high-fat and MC- diet rats when compared to control. Protein expression of OATP1a1 was significantly decreased in high-fat animals, while OATP1a1 and OATP1b2 expression was significantly lower in MC- rats when compared to control. Liver tissue from high-fat and MC- rats stained positive for IL-1?, a pro-inflammatory cytokine known to decrease expression of NTCP, OATP and OAT transporters, suggesting a plausible mechanism for the observed transporter alterations. These data suggest that different stages of NAFLD result in altered hepatic uptake transporter expression that can lead to a functional impairment of xenobiotic uptake from the blood. Furthermore, NAFLD may alter the plasma retention time of clinically relevant drugs that are reliant on these transporters and may increase the potential drug toxicity. PMID:19358839

  4. Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.

    PubMed

    Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei; Zhou, Zhanxiang

    2013-12-01

    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

  5. Serological response and detection of viraemia in acute hepatitis C virus infection.

    PubMed

    Dourakis, S; Brown, J; Kumar, U; Karayiannis, P; Kernoff, P; Chiba, J; Ohba, H; Miyamura, T; Saito, I; Monjardino, J

    1992-03-01

    The serological response during acute hepatitis C virus (HCV) infection was examined by enzyme-linked immunosorbent assay (ELISA) in sequential serum samples from 13 haemophiliacs following their first exposure to factor VIII concentrates contaminated with HCV. The commercially available C100-3 peptide and a new 22 kDa recombinant protein (p22) encoded by the nucleocapsid region of the viral genome were used for antibody detection, whilst a nested polymerase chain reaction (PCR) method was used for the detection of viraemia. In addition, eight sporadic cases of acute HCV infection were studied. The results in haemophiliacs demonstrated that seroconversion to the C100-3 antigen occurred in only one-third of the patients within 12 weeks of disease onset, but all of the patients had a diagnostic serological response to p22 during this phase of the disease. The new test was positive in all the sporadic cases at a time when the commercially available test was negative. Although PCR offers a sensitive method for the detection of recent HCV infection, the complex methodology makes it unsuitable for diagnostic laboratories. The new ELISA test with p22 may therefore have a useful diagnostic role in acute disease. PMID:1380025

  6. Acute and chronic aquatic toxicity structure-activity relationships for alcohol ethoxylates.

    PubMed

    Morrall, D D; Belanger, S E; Dunphy, J C

    2003-11-01

    Acute and chronic toxicity tests using the cladoceran Daphnia magna were conducted on several alcohol ethoxylate surfactants. Exposure and homologue distributions were confirmed using specific analytical methods. These data were used to test currently available acute structure-activity relationships (SARs) and to develop a new chronic SAR to extrapolate test data to effluent or receiving water mixtures. Existing acute SARs adequately predicted the toxicity of these materials with an r(2) of 0.96 based on alkyl chain length and number of ethoxylates and 0.98 based on logK(ow). The additional chronic toxicity data allowed for development of a chronic SAR based on logK(ow) and produced an r(2) of 0.93. Slopes of new and published acute, chronic, and mesocosm SARs based on logK(ow) ranged from -0.61 to -0.87. These new data and refined SARs will assist in the toxicity prediction of mixtures in the environment. PMID:14575678

  7. 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

  8. Gender Differences in Acute Alcohol Effects on Self-Regulation of Arousal in Response to Emotional and Alcohol-Related Picture Cues

    PubMed Central

    Udo, Tomoko; Bates, Marsha E.; Mun, Eun Young; Vaschillo, Evgeny G.; Vaschillo, Bronya; Lehrer, Paul; Ray, Suchismita

    2010-01-01

    Basic mechanisms through which men and women self-regulate arousal have received little attention in human experimental addiction research although stress-response-dampening and craving theories suggest an important role of emotional arousal in motivating alcohol use. This study examined gender differences in the effects of acute alcohol intoxication on psychophysiological and self-reported arousal in response to emotionally negative, positive, and neutral, and alcohol-related, picture cues. Thirty-six social drinkers (16 women) were randomly assigned to an alcohol, placebo, or control beverage group, and exposed to picture cues every 10 s (0.1 Hz presentation frequency). Psychophysiological arousal was assessed via a 0.1-Hz heart rate variability (HRV) index. A statistically significant beverage group-by-gender interaction effect on psychophysiological, but not self-reported, arousal was found. 0.1-Hz HRV responses to picture cues were suppressed by alcohol only in men. This gender-specific suppression pattern did not differ significantly across picture cue types. There were no significant gender differences in the placebo or control group. Greater dampening of arousal by alcohol intoxication in men, compared to women, may contribute to men's greater tendency to use alcohol to cope with stress. PMID:19586136

  9. 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

  10. Immune responses to the hepatitis B surface antigen and liver-specific lipoprotein in acute type B hepatitis.

    PubMed Central

    Lee, W M; Reed, W D; Osman, C G; Vahrman, J; Zuckerman, A J; Eddleston, A L; Williams, R

    1977-01-01

    A serial prospective study of cellular immunity to HBsAg and liver-specific membrane lipoprotein was undertaken in 21 adults with acute hepatitis type B. Cellular immunity to HBsAg as determined by leucocyte migration inhibition with partially purified HBsAg as antigen was detected in all the patients during the recovery phase of the illness and was already detectable at the time of admission in 13 (62%) of the cases. In five of the remaining eight the titre of HBsAg in the serum at this time was high and in the whole series there was an inverse correlation between the degree of migration inhibition on admission and the peak HBsAg titre suggesting that antigen or possibly antigen/antibody complexes might be interfering with the demonstration of cellular immunity in vitro. Using a combination of minimum migration index recorded during the recovery period peak HBsAg titre, it was possible to compute the peak aspartate aminotransferase level with reasonable accuracy, a finding consistent with the hypothesis that the severity of the illness is related to both the number of infected hepatocytes and the vigour of the immune response to HBsAg. Evidence of an immune response to the liver-specific hepatocyte membrane lipoprotein was present in 50% of the patients tested at the time of admission, but was transient, having disappeared in every case by four weeks. The minimum migration index recorded with HBsAg as antigen was significantly lower in those with detectable sensitisation to the lipoprotein and it is possible that this autoimmune reaction is also generated by the interaction of T cells with viral antigenic determinants on the liver cell surface. PMID:856683

  11. Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A

    PubMed Central

    Chang, Hyo Jeong; Cho, Sung Gyun; Oh, Tae Hoon; Jeon, Tae Joo; Shin, Won Chang; Choi, Won Choong

    2014-01-01

    Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA. PMID:25032187

  12. Immune responses during acute and chronic infection with hepatitis C virus

    PubMed Central

    Ishii, Shigeaki; Koziel, Margaret James

    2008-01-01

    Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection. PMID:18514579

  13. Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A.

    PubMed

    Chang, Hyo Jeong; Sinn, Dong Hyun; Cho, Sung Gyun; Oh, Tae Hoon; Jeon, Tae Joo; Shin, Won Chang; Choi, Won Choong

    2014-06-01

    Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA. PMID:25032187

  14. Loss of GABAB binding sites in the cerebral cortex of rats with acute hepatic encephalopathy.

    PubMed

    Oja, S S; Saransaari, P; Wysmyk, U; Albrecht, J

    1993-12-01

    The binding of [3H]GABA to GABAA and GABAB binding sites was measured in cerebral cortical membranes derived from control rats and rats with acute hepatic encephalopathy (HE) induced with a hepatotoxin, thioacetamide. HE did not affect the kinetic parameters (KD and Bmax) for the GABAA binding site. However, HE decreased Bmax (but not KD) for the GABAB binding site to 32% of the control level, indicating a substantial loss of GABAB receptors. Since GABAB receptors control the cerebral cortical release of the amino acid neurotransmitters glutamate and GABA, the loss of GABAB receptors is likely to contribute to the array of disturbances of glutamatergic and GABAergic neurotransmission known to accompany HE. PMID:8111641

  15. Alcohol

    MedlinePLUS

    ... older From a very young age, kids see advertising messages showing beautiful people enjoying life — and alcohol. ... to risk feeling rejected or left out. Different strategies for turning down alcohol work for different people. ...

  16. Dynamic Changes of Lipopolysaccharide Levels in Different Phases of Acute on Chronic Hepatitis B Liver Failure

    PubMed Central

    Zhang, Wei; Zheng, Yubao; Peng, Liang; Deng, Hong; Chen, Youming; Chen, Lubiao; Chen, Sui; Zhang, Min; Gao, Zhiliang

    2012-01-01

    Background High serum levels of lipopolysaccharide (LPS) with LPS-MD-2/TLR4 complex activated NF-kb and cytokine cause hepatic necrosis in animal models. We investigated the dynamic changes of LPS levels in patients with acute on chronic hepatitis B liver failure (ACHBLF). Methods We enrolled ACHBLF patients for a 12-week study. Patients’ LPS levels were measured along with 10 healthy controls. Patients on supportive care and recovered without intervention(s) were analyzed. Patients’ LPS levels during the disease progression phase, peak phase, and remission phase were compared with healthy controls. Results Among 30 patients enrolled, 25 who received interventions or expired during the study period were excluded from the analysis, five patients on supportive care who completed the study were analyzed. Significant abnormal distributions of LPS levels were observed in patients in different phases (0.0168±0.0101 in progression phase; 0.0960±0.0680 in peak phase; 0.0249±0.0365 in remission phase; and 0.0201±0.0146 in controls; respectively, p<0.05). The highest level of LPS was in the peak phase and significantly elevated when compared to controls (0.0201±0.0146 vs. 0.0960±0.0680, p?=?0.007). There were no statistically significant differences in LPS levels between healthy controls and subjects in the progression phase or remission phase. Dynamic changes of LPS were correlated with MELD-Na in the progression phase (p?=?0.01, R?=?0.876) and in the peak phase (p?=?0.000, R?=??1.00). Conclusions Significant abnormal distributions of LPS levels were observed in ACHBLF with the highest level in the peak phase. The dynamic changes of LPS were correlated with disease severity and suggested LPS causing secondary hepatic injury. PMID:23185336

  17. Factors affecting the changes in molecular epidemiology of acute hepatitis B in a Southern Italian area.

    PubMed

    Coppola, N; Masiello, A; Tonziello, G; Pisapia, R; Pisaturo, M; Sagnelli, C; Messina, V; Iodice, V; Sagnelli, E

    2010-07-01

    To explore changes in molecular epidemiology of acute viral hepatitis B (AVH-B), hepatitis B virus (HBV) genotypes were determined by direct sequencing of the Pre-S-S region in 123 consecutive patients, with AVH-B observed in Naples or its surroundings in the last decade (group AVH-B) and in 123 HBV chronic carriers [chronic carrier of HBV (CC-B) group] from the same areas, who had been hepatitis B surface antigen-positive for more than 10 years. Genotype D was less frequently detected in patients with AVH-B than in those in the CC-B group (76.4%vs 97.5%, P < 0.0001). In the AVH-B group, intravenous drug addiction (IVDA) was the prevalent risk factor (55.3%) for acquiring HBV in the 94 patients with HBV genotype D, but it was rarely recorded (6.9%) in the 29 patients with genotypes non-D (P < 0.0001); unsafe sexual intercourse was prevalent in patients with genotype non-D (72.3%) and less frequent in those with genotype D (28.8%, P < 0.005). In the AVH-B group, the prevalence of non-D genotypes increased during the observation period from 11.1% in 1999-2003 to 41.1% in 2004-2008 (P < 0.0005), paralleling the increase in the prevalence of patients with unsafe sexual intercourse; similarly, the progressive decrease in IVDA paralleled the decrease in the prevalence of genotype D (from 88.3% in 1999-2003 to 11.7% in 2004-2008). The prevalence of HBV non-D genotypes recorded in the last 10 years in AVH-B in this area shows a progressive increase, most probably because of recent changes in HBV epidemiology, namely, the HBV mass vaccination campaign and increased immigration from areas with high HBV endemicity. PMID:19780943

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

    PubMed Central

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

    2011-01-01

    AIM: To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed. Their general conditions and survival were analyzed by survival analysis and Cox regression analysis. RESULTS: A total of 190 patients were included in this study. The overall 1-year survival rate was 57.6%. Patients not treated with antiviral drugs had a significantly higher mortality [relative risk (RR) = 0.609, P = 0.014]. The highest risk of death in patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P =0.026), while other significant factors were electrolyte disturbances (RR = 2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001). CONCLUSION: Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte disturbances, and HE also affect patient survival. PMID:21876637

  19. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure.

    PubMed

    Mhanni, A A; Chan, A; Collison, M; Seifert, B; Lehotay, D C; Sokoro, Ah; Huynh, H Q; Greenberg, C R

    2008-03-01

    We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving. PMID:18376250

  20. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease.

    PubMed

    Gillis, J H; Satapathy, S K; Parsa, L; Sylvestre, P B; Dbouk, N

    2015-01-01

    Acute sickle hepatic crisis (ASHC) has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS) sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease. PMID:25789194

  1. Alcohol

    PubMed Central

    Nathani, Milankumar; Jabeen, Shahgufta; Yazdani, Ijlal; Mouton, Charles D.; Bailey, Rahn K.; Mahr, Mona; Pate, Rebecca J.; Riley, Wayne J.

    2013-01-01

    Suicide is a major public health problem in the United States as well as around the world. The significant role that alcohol plays in suicidality is well known and accepted in the scientific community. The use of alcohol does not necessarily lead to suicide, but through its action and effects, alcohol is an important proximal risk factor for suicidal behavior. There is very little data showing how and why alcohol exerts such tremendous influence and “lubricates the gears” to propel the act of committing suicide. This article will elucidate the complex relationship between alcohol and suicide and how alcohol use can lead to suicide. The article also describes how alcohol affects brain neurophysiology in regards to suicidal behavior. PMID:23440995

  2. Hepatitis

    MedlinePLUS

    ... Disease Dementia Hospitalization & Palliative Care Related Topics on AIDS.gov Combating the Silent Epidemic of Viral Hepatitis: ... Adults and Adolescents Last revised: 05/07/2014 AIDS.gov HIV/AIDS Basics • Federal Resources • Using New ...

  3. Hepatitis

    MedlinePLUS

    ... men, hepatitis A can be spread by direct anal/oral contact (rimming) or by contact with fingers, ... to protect yourself include avoiding rimming and other anal and oral contact. While condom use is essential ...

  4. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    SciTech Connect

    Chen Bo [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027 (China); State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Science, Beijing 100101 (China); Xia Jing; Li Guangxing [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027 (China); Zhou Yifeng, E-mail: zhouy@ustc.edu.c [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027 (China); State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Science, Beijing 100101 (China)

    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.

  5. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    Microsoft Academic Search

    Bo Chen; Jing Xia; Guangxing Li; Yifeng Zhou

    2010-01-01

    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

  6. Acute effects of alcohol on feedback processing and outcome evaluation during risky decision-making: an ERP study

    Microsoft Academic Search

    Anja S. Euser; Catharina S. van Meel; Michelle Snelleman; Ingmar H. A. Franken

    2011-01-01

    Rationale  Although risky decision-making is one of the hallmarks of alcohol use disorders, relatively little is known about the acute\\u000a psychopharmacological effects of alcohol on decision-making processes.\\u000a \\u000a \\u000a \\u000a \\u000a Objective  The present study investigated the acute effects of alcohol on neural mechanisms underlying feedback processing and outcome\\u000a evaluation during risky decision-making, using event-related brain potentials (ERPs).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  ERPs elicited by positive and negative feedback were

  7. 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...

  8. 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-? 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

  9. 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.

  10. Successful management of hepatic mucormycosis in an acute lymphoblastic leukaemia patient: a case report and review of the literature.

    PubMed

    Tuysuz, Gulen; Ozdemir, Nihal; Senyuz, Osman Faruk; Emre, Senol; Kantarcioglu, Serda; Adaletli, Ibrahim; Kepil, Nuray; Tutuncu, Cigdem; Celkan, Tiraje

    2014-08-01

    We present a case of hepatic mucormycosis in a 9-year-old boy with acute lymphoblastic leukaemia. Despite long-term use of combined liposomal amphotericin B and posaconazole therapy, the lesion persisted and could only be treated by surgical excision. After surgery, antifungal treatment was continued with posaconazole. On follow-up, the patient had two episodes of ascending cholangitis which were responsive to intravenous antibiotics. He is doing well at the moment in remission for 2.5 years. Mucormycosis was long regarded as a fatal infection with poor prognosis. With early medical and surgical management, survival rates increase. Isolated hepatic mucormycosis is rare and only seven cases were reported in the literature up to now. We wanted to emphasise the role of early surgery in patients with hepatic mucormycosis in view of the literature. PMID:24635874

  11. Symptomatic Acute Hepatitis C in Egypt: Diagnosis, Spontaneous Viral Clearance, and Delayed Treatment with 12 Weeks of Pegylated Interferon Alfa-2a

    PubMed Central

    Sharaf Eldin, Noha; Ismail, Soheir; Mansour, Hala; Rekacewicz, Claire; El-Houssinie, Moustafa; El-Kafrawy, Sherif; El Aidi, Saeed; Abdel-Hamid, Mohamed; Esmat, Gamal; Pol, Stanislas; Fontanet, Arnaud; Mohamed, Mostafa K.

    2008-01-01

    Background and Objectives The aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously. Methods Patients with symptomatic acute hepatitis C were recruited from two “fever hospitals” in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 µg/week). Results Between May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%–43.2%]) at three months and 41.5% (95%CI [33.0%–51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4–6 months after onset of symptoms was 15/17?=?88.2% (95%CI [63.6%–98.5%]). Conclusion Spontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C. PMID:19115010

  12. Detection of functionally altered hepatitis C virus-specific CD4 + T cells in acute and chronic hepatitis C

    Microsoft Academic Search

    Axel Ulsenheimer; J. Tilman Gerlach; Norbert H. Gruener; Maria-Christina Jung; Carl-Albrecht Schirren; Winfried Schraut; Reinhart Zachoval; Gerd R. Pape; Helmut M. Diepolder

    2003-01-01

    Chronic hepatitis C is characterized by a weak or absent hepatitis C virus (HCV)-specific CD4+ T-cell response in terms of antigen-specific proliferation or interferon gamma (IFN-?) secretion. To clarify whether this is due to the absence or functional impairment of antigen-specific CD4+ T cells we developed an assay that relies on the induced expression of the T-cell activation marker CD25

  13. 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

  14. 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

  15. The changing epidemiology of acute type B hepatitis: Results of an 11-year prospective study in padua (Northern Italy)

    Microsoft Academic Search

    F. Bortolotti; N. Noventa; P. Cadrobbi; C. Crivellaro; F. Menenghetti; M. Carretta; A. Stivanello; A. De Rossi

    1989-01-01

    Summary The epidemiological pattern of acute type B hepatitis has been investigated in 1,107 consecutive patients during an 11-year prospective study conducted in Padua (Northern Italy) between 1978 and 1988. Remarkable changes were observed: 1) the attack rate of the disease increased significantly (p5 inhabitants) and 1982 (29\\/105 inhabitants), particularly in male subjects and in the 15–19-year age group. The

  16. Glutathione S-transferase A1 (GSTA1) release, an early indicator of acute hepatic injury in mice.

    PubMed

    Liu, Fangping; Lin, Yuexia; Li, Zhi; Ma, Xin; Han, Qing; Liu, Yingshu; Zhou, Qiong; Liu, Jingli; Li, Rui; Li, Jichang; Gao, Li

    2014-09-01

    Three acute hepatic injury models (a CCl4-induced model, APAP-induced model and ethanol-induced model) in mice were used to study the importance of GSTA1 in acute hepatic injury by comparison with a standard enzyme marker, alanine aminotransferase (ALT). GSTA1 release was demonstrated to be an earlier and more sensitive indicator of hepatotoxicity than was ALT. Significant increases in GSTA1 were detected at 2 h after CCl4 exposure, while ALT was undetected at this time. GSTA1 was also a more sensitive indicator of hepatotoxicity than ALT after 6 h. In the APAP and ethanol models, GSTA1 was markedly increased earlier than ALT, at 2 h post exposure. The release of GSTA1 was significantly increased at a dose of 12.5 mg/kg (CCl4 model), 100 mg/kg (APAP model) and 10 ml/kg (ethanol model), the lowest exposure concentration for each model. In contrast, AST release was not statistically significant. These results suggest that GSTA1 can be detected at low concentrations during the early stages of acute hepatic injury and that GSTA1 is a more sensitive and more accurate indicator than ALT. PMID:24964013

  17. Endovascular Treatment of Acute Arterial Hemorrhage in Trauma Patients Using Ethylene Vinyl Alcohol Copolymer (Onyx)

    SciTech Connect

    Mueller-Wille, R., E-mail: rene.mueller-wille@klinik.uni-regensburg.de; Heiss, P., E-mail: peter.heiss@klinik.uni-regensburg.de [University Medical Center Regensburg, Department of Radiology (Germany); Herold, T., E-mail: thomas.herold@helios-kliniken.de [Helios Klinikum Berlin-Buch, Department of Radiology (Germany); Jung, E. M., E-mail: ernst-michael.jung@klinik.uni-regensburg.de; Schreyer, A. G., E-mail: andreas.schreyer@klinik.uni-regensburg.de; Hamer, O. W., E-mail: okka.hamer@klinik.uni-regensburg.de; Rennert, J., E-mail: janine.rennert@klinik.uni-regensburg.de; Hoffstetter, P., E-mail: P.hoffstetter@asklepios.com; Stroszczynski, C., E-mail: christian.stros@klinik.uni-regensburg.de [University Medical Center Regensburg, Department of Radiology (Germany); Zorger, N., E-mail: Niels.Zorger@barmherzige-regensburg.de [Krankenhaus Barmherzige Brueder Regensburg, Department of Radiology (Germany)

    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.

  18. 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; Chang, Kyong-Mi

    2014-01-01

    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 (ALT) elevation with anti-HCV seroconversion, HCV-RNA fluctuations above 1 log and/or recent high-risk exposure without prior HCV infection, excluding those with HIV infection. Clinical and therapeutic outcomes were monitored for at least 6 months. Results 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and Caucasians (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% healthcare-associated, 3% sexual and 45% unknown) and wide variations in peak ALT (143-3435 U/L) and total bilirubin levels (0.4-19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27% whereas 50% received IFN?-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% ANA, 69% ASMA) or autoimmune features; 3) delayed spontaneous viral clearance in 2 patients; 4) rapid cirrhosis progression in 2 patients. Conclusions AHCV is a heterogeneous 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

  19. Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure

    PubMed Central

    Saracyn, Marek; Brytan, Marek; Zdanowski, Robert; Z?bkowski, Tomasz; Dyrla, Przemys?aw; Patera, Janusz; Wojtu?, Stanis?aw; Koz?owski, Wojciech; Wa?kowicz, Zofia

    2014-01-01

    AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF). METHODS: An experimental rat model of galactosamine-induced AHF was used. An inhibitor of NO synthase, nitroarginine methyl ester, or an NO donor, arginine, were administered at various doses prior to or after the induction of AHF. RESULTS: All tested groups developed AHF. Following inhibition of the endogenous NO pathway, most liver parameters improved, regardless of the inhibitor dose before the induction of liver damage, and depending on the inhibitor dose after liver damage. Prophylactic administration of the inhibitor was more effective in improving liver function parameters than administration of the inhibitor after liver damage. An attempt to activate the endogenous NO pathway prior to the induction of liver damage did not change the observed liver function parameters. Stimulation of the endogenous NO pathway after liver damage, regardless of the NO donor dose used, improved most liver function parameters. CONCLUSION: The endogenous NO pathway plays an important role in the development of experimental galactosamine-induced AHF. PMID:25516652

  20. Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

    PubMed

    Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

    2014-11-01

    The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-? were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-? and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT. PMID:25004996

  1. 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

  2. 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 ?-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

  3. Alcohol

    Microsoft Academic Search

    William E. M. Lands

    \\u000a \\u000a \\u000a Key Points\\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Excessive alcohol consumption contributes to 4 of the 10 leading causes of death in the United States.\\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Alcohol consumption is split, with 33% of the population consuming 95% of the alcoholic beverages and 33% abstaining. The\\u000a US population median intake is much less than the average (mean) intake.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a An increase in average alcohol intake could

  4. Circulating proinflammatory cytokines (IL-1 beta, TNF-alpha, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis.

    PubMed Central

    Sekiyama, K D; Yoshiba, M; Thomson, A W

    1994-01-01

    Fulminant hepatic failure (FHF) is characterized by massive necroinflammation of the liver tissue and is associated with high mortality. Serum concentrations of IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 receptor antagonist (IL-1Ra) were measured in 30 patients with FHF and in 23 patients with acute hepatitis (AH) before start of treatment and in 23 healthy controls. Levels of all four molecules were increased significantly in FHF compared with AH, in which values were higher than in the healthy controls. High serum levels of IL-1 beta and a significantly reduced ratio of IL-1Ra to IL-1 beta (IL-1Ra/IL-1 beta) were observed in FHF patients who subsequently died compared with subjects who survived. TNF-alpha and IL-6 concentrations were correlated with levels of human hepatocyte growth factor (hHGF), an index of hepatocyte regeneration. Although serum cytokine levels varied considerably between patients within each group studied, it is suggested that the striking elevation in proinflammatory cytokine levels in FHF may reflect both the insufficiency of hepatitis virus elimination and a failure to control a vicious cytokine cascade leading to overwhelming hepatocyte destruction rather than regeneration. The high cytokine levels observed in these patients and the significantly elevated IL-1Ra/IL-1 beta ratio in FHF patients who survived compared with those who did not suggest the possible therapeutic use of cytokine antagonists for the control of this life-threatening disease. PMID:7923888

  5. How CAGE, RAPS4-QF, and AUDIT Can Help Practitioners for Patients Admitted with Acute Alcohol Intoxication in Emergency Departments?

    PubMed Central

    Brousse, Georges; Arnaud, Benjamin; Geneste, Julie; Pereira, Bruno; De Chazeron, Ingrid; Teissedre, Frederique; Perrier, Christophe; Schwan, Raymund; Malet, Laurent; Schmidt, Jeannot; Llorca, Pierre Michel; Cherpitel, Cheryl J.

    2014-01-01

    Aims: To help clinicians to identify the severity of alcohol use disorders (AUDs) from optimal thresholds found for recommended scales. Especially, taking account of the high prevalence of alcohol dependence among patients admitted to the emergency department (ED) for acute alcohol intoxication (AAI), we propose to define thresholds of severity of dependence based on the AUDIT score. Methods: All patients admitted to the ED with AAI (blood alcohol level >0.8?g/L), in a 2-month period, were assessed using the CAGE, RAPS-QF, and AUDIT, with the alcohol dependence/abuse section of the mini international neuropsychiatric interview (MINI) used as the gold standard. To explore the relation between the AUDIT and the MINI the sum of the positive items on the MINI (dependence) as a quantitative variable and as an ordinal parameter were analyzed. From the threshold score found for each scale we proposed intervals of severity of AUDs. Results: The mean age of the sample (122 males, 42 females) was 46?years. Approximately 12% of the patients were identified with alcohol abuse and 78% with dependence (DSM-IV). Cut points were determined for the AUDIT in order to distinguish mild and moderate dependence from severe dependence. A strategy of intervention based on levels of severity of AUD was proposed. Conclusion: Different thresholds proposed for the CAGE, RAPS4-QF, and AUDIT could be used to guide the choice of intervention for a patient: brief intervention, brief negotiation interviewing, or longer more intensive motivational intervention. PMID:25009509

  6. 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

  7. Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naïve patients with chronic hepatitis B infection

    PubMed Central

    Chung, Won Gil; Choe, Young Gil; Seok, Hyo Sun; Chon, Chang Wook; Cho, Yong Kyun; Kim, Byung Ik; Koh, Young Yool

    2012-01-01

    Background/Aims The aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV) therapy in chronic hepatitis B (CHB) patients. Methods The medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI) values and Alcohol Use Disorders Identification Test (AUDIT) scores were obtained at 6 months after the initiation of ETV (0.5 mg daily) treatment. Results A BMI of 25 kg/m2 or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3%) were obese and 17 (19.3%) were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT) normalization, and hepatitis B virus (HBV)-DNA negativity (<300 copies/mL) at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033). Conclusions Obesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users. PMID:22893870

  8. Alcohol Use Reduction Program in Methadone Maintained Individuals with Hepatitis C Virus Infection

    Microsoft Academic Search

    Adeline Nyamathi; Viviane de Castro; Donna McNeese-Smith; Kamala Nyamathi; Steven Shoptaw; Mary Marfisee; Farinaz Khalilifard; Allan Cohen

    2008-01-01

    The purpose of this article was to investigate the personal and social barriers experienced by methadone maintained clients when seeking treatment for alcohol abuse along with strategies for engaging such clients in treatment programs. A qualitative design using semi-structured focus groups was used to obtain the perspectives of 41 methadone-maintained clients in Los Angeles, California. Sessions were recorded, transcribed, and

  9. Goal-related outcome after acute alcohol-pancreatitis -- a two-year follow-up study.

    PubMed

    Lappalainen-Lehto, Riitta; Koistinen, Noora; Aalto, Mauri; Huhtala, Heini; Sand, Juhani; Nordback, Isto; Seppä, Kaija

    2013-12-01

    The aim of this study was to find out if an acute pancreatitis leads the patients to reduce their alcohol consumption and if there are factors predicting the outcome. We also observed which factors affected the choice of patient's personal drinking goal, e.g., abstinence or moderate drinking, how this goal changed during the follow-up and how the goal affected the change in drinking habits. In 2001-2005, 120 patients treated in Tampere University Hospital for their first alcohol-related acute pancreatitis were interviewed before discharge from the hospital and at the two-year follow-up. All patients had at least one intervention session for their alcohol use. Of the patients 87 (72.5%) completed the study. The alcohol consumption level and its changes, personal drinking goal of the patients, the factors affecting the choice and the changes of the goal were observed. Most (96.4%) of the patients were willing to reduce their drinking. At follow-up, 34 (40.5%) patients succeeded in reducing their alcohol consumption under the pre-set moderate drinking level. The only factor predicting alcohol use was the number of hospitalization days due to the acute alcohol-related pancreatitis (p=0.015). Those who chose abstinence seemed to succeed more often in stopping drinking or reducing their drinking below risk levels as compared to those with moderation goal (47.9% vs. 28.6%, p=0.075). The only abstinence-goal predicting factor was the concern of the relatives, friends or doctors (p=0.001). All 6 patients who needed intensive care chose abstinence-goal. During the follow-up period the goal changed. At baseline, the majority chose abstinence but two years after pancreatitis, the majority was striving for moderate drinking. A serious illness seems to be a good opportunity to change and to motivate patients. Even if abstinence is recommended to patients with alcohol-related pancreatitis, communication of individual goals is important in the motivation process of the patients. PMID:24018221

  10. 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

  11. PPAR? 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 PPAR? 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 PPAR? 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/GSK3?, and reduced expression of insulin responsive genes mediating energy metabolism and tissue remodeling. PPAR? agonist treatment reduced ethanol-mediated hepatic injury, oxidative stress, lipid peroxidation, and insulin resistance, increased signaling through PI3K/Akt/GSK3?, and enhanced the regenerative response to partial hepatectomy. Conclusions PPAR? 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

  12. Hepatitis E outbreak on cruise ship.

    PubMed

    Said, Bengü; Ijaz, Samreen; Kafatos, George; Booth, Linda; Thomas, H Lucy; Walsh, Amanda; Ramsay, Mary; Morgan, Dilys

    2009-11-01

    In 2008, acute hepatitis E infection was confirmed in 4 passengers returning to the United Kingdom after a world cruise. Epidemiologic investigation showed that of 789 persons who provided blood samples, 195 (25%) were seropositive, 33 (4%) had immunoglobulin [Ig] M levels consistent with recent acute infection (11 of these persons were symptomatic), and 162 (21%) had IgG only, consistent with past infection. Passenger mean age was 68 years. Most (426/789, 54%) passengers were female, yet most with acute infection (25/33, 76%) were male. Sequencing of RNA from 3 case-patients identified hepatitis E virus genotype 3, closely homologous to genotype 3 viruses from Europe. Significant association with acute infection was found for being male, drinking alcohol, and consuming shellfish while on board (odds ratio 4.27, 95% confidence interval 1.23-26.94, p = 0.019). This was probably a common-source foodborne outbreak. PMID:19891860

  13. Hepatitis E Outbreak on Cruise Ship

    PubMed Central

    Ijaz, Samreen; Kafatos, George; Booth, Linda; Thomas, H. Lucy; Walsh, Amanda; Ramsay, Mary; Morgan, Dilys

    2009-01-01

    In 2008, acute hepatitis E infection was confirmed in 4 passengers returning to the United Kingdom after a world cruise. Epidemiologic investigation showed that of 789 persons who provided blood samples, 195 (25%) were seropositive, 33 (4%) had immunoglobulin [Ig] M levels consistent with recent acute infection (11 of these persons were symptomatic), and 162 (21%) had IgG only, consistent with past infection. Passenger mean age was 68 years. Most (426/789, 54%) passengers were female, yet most with acute infection (25/33, 76%) were male. Sequencing of RNA from 3 case-patients identified hepatitis E virus genotype 3, closely homologous to genotype 3 viruses from Europe. Significant association with acute infection was found for being male, drinking alcohol, and consuming shellfish while on board (odds ratio 4.27, 95% confidence interval 1.23–26.94, p = 0.019). This was probably a common-source foodborne outbreak. PMID:19891860

  14. 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. [Shell Development Co., Houston, TX (United States)

    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.

  15. Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

    PubMed Central

    Philips, Cyriac Abby; Sarin, Shiv Kumar

    2014-01-01

    Acute on chronic liver failure (ACLF) is a disease entity with a high mortality rate. The acute event arises from drugs and toxins, viral infections, bacterial sepsis, interventions (both surgical and non-surgical) and vascular events on top of a known or occult chronic liver disease. ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition; the high mortality of which can be managed in the wake of new potent antiviral therapy. For example, lamivudine and entecavir use has shown definite short-term survival benefits, even though drug resistance is a concern in the former. The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction. Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients. This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B, thereby providing an algorithm in management of such patients. PMID:25473156

  16. Hepatitis C virus infection in children treated for acute lymphoblastic leukemia.

    PubMed

    Aricò, M; Maggiore, G; Silini, E; Bono, F; Viganò, C; Cerino, A; Mondelli, M U

    1994-11-01

    We studied 102 consecutive subjects after their completion of acute lymphoblastic leukemia (ALL)-directed chemotherapy, for evidence of hepatitis C virus (HCV) infection by enzyme immunoassay 2 and 3, second generation recombinant immunoblot assay and reverse transcription-polymerase chain reaction (PCR) for detection of circulating HCV-RNA. Forty-four patients (43%) had evidence of exposure to HCV; 30 of these were anti-HCV+. Of the 23 patients who were positive for both anti-HCV and HCV-RNA, 16 (69%) had a moderate increase in serum alanine aminotransferase (ALT) activity without clinical signs of liver disease. Fourteen patients were seronegative despite the presence of HCV-RNA in the serum. The proportion of different HCV genotypes was not significantly different from other anti-HCV+ patient groups. Although half of the patients with genotype III had normal ALT value, patients with normal ALT levels were represented in all genotype groups. Our study documents the prevalence of HCV infection in childhood ALL survivors, which is responsible for the majority of cases of non-B chronic liver disease in these patients. Whereas serologic screening identifies over 70% of patients with ongoing HCV infection, real HCV infection may be present even in the absence of a detectable humoral immune response to the virus. Based on this observation, determination of HCV-RNA by PCR should be recommended in patients in prolonged remission even if they test negative on serological assay. Normal ALT levels do not exclude the presence of HCV infection because the values were repeatedly normal in over half of our viremic patients. PMID:7949165

  17. Molecular Pathways Differentiate Hepatitis C Virus (HCV) Recurrence from Acute Cellular Rejection in HCV Liver Recipients

    PubMed Central

    Gehrau, Ricardo; Maluf, Daniel; Archer, Kellie; Stravitz, Richard; Suh, Jihee; Le, Ngoc; Mas, Valeria

    2011-01-01

    Acute cellular rejection (ACR) and hepatitis C virus (HCV) recurrence (HCVrec) are common complications after liver transplantation (LT) in HCV patients, who share common clinical and histological features, making a differential diagnosis difficult. Fifty-three liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n = 32) and a validation set (n = 19). Two no-HCV-ACR samples from LT recipients were also included. Probe set intensity values were obtained using the robust multiarray average method (RMA) method. Analysis of variance identified statistically differentially expressed genes (P ? 0.005). The limma package was used to fit the mixed-effects models using a restricted maximum likelihood procedure. The last absolute shrinkage and selection operator (LASSO) model was fit with HCVrec versus ACR as the dependent variable predicted. N-fold cross-validation was performed to provide an unbiased estimate of generalization error. A total of 179 probe sets were differentially expressed among groups, with 71 exclusive genes between HCVrec and HCV-ACR. No differences were found within ACR group (HCV-ACR vs. no-HCV-ACR). Supervised clustering analysis displayed two clearly independent groups, and no-HCV-ACR clustered within HCV-ACR. HCVrec-related genes were associated with a cytotoxic T-cell profile, and HCV-ACR–related genes were associated with the inflammatory response. The best-fitting LASSO model classifier accuracy, including 15 genes, has an accuracy of 100% in the training set. N-fold cross-validation accuracy was 78.1%, and sensitivity, specificity and positive and negative predictive values were 50.0%, 90.9%, 71.4% and 80.0%, respectively. Arginase type II (ARG2), ethylmalonic encephalopathy 1 (ETHE1), transmembrane protein 176A (TMEM176A) and TMEM176B genes were significantly confirmed in the validation set. A molecular signature capable of distinguishing HCVrec and ACR in HCV LT recipients was identified and validated. PMID:21519635

  18. Molecular pathways differentiate hepatitis C virus (HCV) recurrence from acute cellular rejection in HCV liver recipients.

    PubMed

    Gehrau, Ricardo; Maluf, Daniel; Archer, Kellie; Stravitz, Richard; Suh, Jihee; Le, Ngoc; Mas, Valeria

    2011-01-01

    Acute cellular rejection (ACR) and hepatitis C virus (HCV) recurrence (HCVrec) are common complications after liver transplantation (LT) in HCV patients, who share common clinical and histological features, making a differential diagnosis difficult. Fifty-three liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n = 32) and a validation set (n = 19). Two no-HCV-ACR samples from LT recipients were also included. Probe set intensity values were obtained using the robust multiarray average method (RMA) method. Analysis of variance identified statistically differentially expressed genes (P ? 0.005). The limma package was used to fit the mixed-effects models using a restricted maximum likelihood procedure. The last absolute shrinkage and selection operator (LASSO) model was fit with HCVrec versus ACR as the dependent variable predicted. N-fold cross-validation was performed to provide an unbiased estimate of generalization error. A total of 179 probe sets were differentially expressed among groups, with 71 exclusive genes between HCVrec and HCV-ACR. No differences were found within ACR group (HCV-ACR vs. no-HCV-ACR). Supervised clustering analysis displayed two clearly independent groups, and no-HCV-ACR clustered within HCV-ACR. HCVrec-related genes were associated with a cytotoxic T-cell profile, and HCV-ACR-related genes were associated with the inflammatory response. The best-fitting LASSO model classifier accuracy, including 15 genes, has an accuracy of 100% in the training set. N-fold cross-validation accuracy was 78.1%, and sensitivity, specificity and positive and negative predictive values were 50.0%, 90.9%, 71.4% and 80.0%, respectively. Arginase type II (ARG2), ethylmalonic encephalopathy 1 (ETHE1), transmembrane protein 176A (TMEM176A) and TMEM176B genes were significantly confirmed in the validation set. A molecular signature capable of distinguishing HCVrec and ACR in HCV LT recipients was identified and validated. PMID:21519635

  19. A novel prognostic score for acute-on-chronic hepatitis B liver failure.

    PubMed

    Yi, Zhao-Quan; Lu, Meng-Hou; Xu, Xu-Wen; Fu, Xiao-Yu; Tan, De-Ming

    2015-02-01

    Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (? scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930±0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF. PMID:25673199

  20. 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

  1. Alcohol use reduction program in methadone maintained individuals with hepatitis C virus infection.

    PubMed

    Nyamathi, Adeline; de Castro, Viviane; McNeese-Smith, Donna; Nyamathi, Kamala; Shoptaw, Steven; Marfisee, Mary; Khalilifard, Farinaz; Cohen, Allan

    2008-01-01

    The purpose of this article was to investigate the personal and social barriers experienced by methadone maintained clients when seeking treatment for alcohol abuse along with strategies for engaging such clients in treatment programs. A qualitative design using semi-structured focus groups was used to obtain the perspectives of 41 methadone-maintained clients in Los Angeles, California. Sessions were recorded, transcribed, and content-analyzed. Attitudes of health care providers were considered critical factors for engaging clients in treatment programs. Other facilitators included incentives and forms of support (emotional, financial, or material aid), whereas barriers consisted of lack of provider knowledge and insensitivity to acquiring needed resources. Clients also discussed the importance of personal attributes in achieving successful behavioral change, such as personal motivation. The findings suggest that healthcare providers' strategies designed to boost motivation, combined with various types of support, may prove successful in alcohol reduction among methadone-maintained clients. PMID:19042588

  2. 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.

  3. Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

    PubMed Central

    Li, Jian-ping; Gao, Yan; Chu, Shi-feng; Zhang, Zhao; Xia, Cong-yuan; Mou, Zheng; Song, Xiu-yun; He, Wen-bin; Guo, Xiao-feng; Chen, Nai-hong

    2014-01-01

    Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects. Methods: Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and ?-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies. Results: In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 ?mol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and ?-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro. Conclusion: Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes. PMID:24976156

  4. Serum Hepatic Enzyme Activity and Alcohol Drinking Status in Relation to the Prevalence of Metabolic Syndrome in the General Japanese Population

    PubMed Central

    Uemura, Hirokazu; Katsuura-Kamano, Sakurako; Yamaguchi, Miwa; Sawachika, Fusakazu; Arisawa, Kokichi

    2014-01-01

    Background Studies on the combined associations of elevated serum hepatic enzyme activity and alcohol drinking with metabolic syndrome are rare. Our objectives were to evaluate the associations of elevated serum hepatic enzyme activity with the prevalence of metabolic syndrome in the general Japanese population and whether alcohol drinking had a modifying effect on these associations. Methods We conducted a cross-sectional study with 1,027 men and 1,152 women throughout Japan during 2002–2010. Biochemical factors including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in overnight fasting blood, and a survey on lifestyle was conducted by questionnaire. Serum ALT and GGT levels were divided into tertiles in men and women, and their associations with the prevalence of metabolic syndrome were evaluated by logistic regressions. Results Elevated serum ALT and GGT, even within the reference range, were independently associated with increased metabolic syndrome prevalence and were associated with most of its components in both sexes, except for the association between GGT and low high-density lipoprotein (HDL) cholesterol in men. Stratified analyses by alcohol drinking status revealed that within the same tertile category of serum ALT and GGT, subjects classified as alcohol abstainers showed higher adjusted odds ratios for metabolic syndrome prevalence than those classified as regular alcohol drinkers in both sexes. The interaction effects of serum GGT with alcohol drinking status on metabolic syndrome prevalence were significant in both sexes. Conclusions These results suggest that elevated serum ALT and GGT, even within the reference range, are independently associated with increased metabolic syndrome prevalence, especially in alcohol abstainers, in Japanese men and women. PMID:24755715

  5. Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats.

    PubMed

    Alwahsh, Salamah Mohammad; Xu, Min; Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

    2014-01-01

    Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (?3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial ?-oxidation of fatty acids (Cpt1? and Ppar-? expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage. PMID:25101998

  6. Combination of Alcohol and Fructose Exacerbates Metabolic Imbalance in Terms of Hepatic Damage, Dyslipidemia, and Insulin Resistance in Rats

    PubMed Central

    Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

    2014-01-01

    Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (?3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial ?-oxidation of fatty acids (Cpt1? and Ppar-? expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage. PMID:25101998

  7. Liver Regeneration Signature in Hepatitis B Virus (HBV)-Associated Acute Liver Failure Identified by Gene Expression Profiling

    PubMed Central

    Diaz, Giacomo; Kleiner, David E.; Tice, Ashley; Fantola, Giovanni; Zamboni, Fausto; Mishra, Lopa; Farci, Patrizia

    2012-01-01

    Introduction The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC). The dramatic clinical course of acute liver failure (ALF) has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV)-associated ALF. Methods and Findings Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7), whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process. Conclusion Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between liver regeneration and liver cancer. PMID:23185381

  8. A case of lamivudine-sensitive de novo acute hepatitis B induced by rituximab with the CHOP regimen for diffuse large B cell lymphoma

    Microsoft Academic Search

    Toru Takahashi; Tadashi Koike; Shigeo Hashimoto; Tomofumi Miura; Junichiro Nakamura; Satoshi Yamada; Tsutomu Miura; Masahiko Yanagi; Kazuhide Yamazaki; Shogo Okoshi; Yutaka Aoyagi

    2009-01-01

    A case of de novo acute hepatitis B that showed symptoms of general malaise and anorexia during rituximab therapy with the\\u000a CHOP regimen for diffuse large B cell lymphoma is reported. Lamivudine was strikingly effective, showing a rapid recovery\\u000a from liver damage with jaundice. Hepatitis B virus (HBV) DNA in serum became and stayed undetectable even after the withdrawal\\u000a of lamivudine,

  9. Early change in bilirubin levels is an important prognostic factor in severe alcoholic hepatitis treated with prednisolone.

    PubMed

    Mathurin, Philippe; Abdelnour, Marcelle; Ramond, Marie-José; Carbonell, Nicolas; Fartoux, Laetitia; Serfaty, Lawrence; Valla, Dominique; Poupon, Raoul; Chaput, Jean-Claude; Naveau, Sylvie

    2003-12-01

    Early identification of patients with severe (discriminant function >or=32) biopsy-proven alcoholic hepatitis (AH) who are not responding to corticosteroids would be clinically relevant. Our goal was to develop simple criteria that will help physicians to promptly identify nonresponders to corticosteroids. A total of 238 patients were included. We used 6 months survival as an end point because of the rule requiring 6 months for listing alcoholic patients for transplantation. Overall survival at 1 and 6 months was 85% +/- 2.3% and 64.3% +/- 3.3%, respectively. An early change in bilirubin levels (ECBL) at 7 days (defined as bilirubin level at 7 days lower than bilirubin level on the first day of treatment) was observed in 73% of patients. At 7 days, in patients with ECBL, bilirubin decreased (84 +/- 75 micromol/L [4.94 +/- 4.40 mg/dL]), whereas it increased in patients without ECBL (76.5 +/- 77 micromol/L [4.50 +/- 4.54 mg/dL], P <.0001). Ninety-five percent of patients with ECBL continued to have improved liver function during treatment. At 6 months, survival of patients with ECBL was significantly higher than that of patients without ECBL, 82.8% +/- 3.3% versus 23% +/- 5.8%, P <.0001. On multivariate analysis, ECBL, discriminant function and creatinine were independent prognostic variables, and ECBL had the most important prognostic value. In conclusion, ECBL is a very simple predictive factor for identifying nonresponders. A recommendation to discontinue corticosteroids after 7 days in patients without ECBL, suggested by our results, awaits additional confirmation. PMID:14647046

  10. Circulating plasmacytoid dendritic cells in acutely infected patients with hepatitis C virus genotype 4 are normal in number and phenotype.

    PubMed

    Mansour, Hala; Laird, Melissa E; Saleh, Rasha; Casrouge, Armanda; Eldin, Noha Sharaf; El Kafrawy, Sherif; Hamdy, Maha; Decalf, Jérémie; Rosenberg, Brad R; Fontanet, Arnaud; Abdel-Hamid, Mohammed; Mohamed, Mostafa K; Albert, Matthew L; Rafik, Mona

    2010-12-01

    The incidence of hepatitis C virus (HCV) genotype 4 infection in Egypt provides a unique opportunity to study the innate immune response to symptomatic acute HCV infection. We investigated whether plasmacytoid dendritic cells (pDCs) are activated as a result of HCV infection. We demonstrate that, even during symptomatic acute infection, circulating pDCs maintained a similar precursor frequency and resting phenotype, compared with pDCs in healthy individuals. Moreover, stimulation with a Toll-like receptor 9 agonist resulted in an intact inflammatory response. These data support the growing consensus that pDCs are not directly activated by HCV and therefore are viable targets for immunotherapy throughout HCV infection. PMID:20958210

  11. Physicochemical properties, antioxidant activities and protective effect against acute ethanol-induced hepatic injury in mice of foxtail millet (Setaria italica) bran oil.

    PubMed

    Pang, Min; He, Shujian; Wang, Lu; Cao, Xinmin; Cao, Lili; Jiang, Shaotong

    2014-08-01

    This study was designed to investigate physicochemical characterization of the oil extracted from foxtail millet bran (FMBO), and the antioxidant and hepatoprotective effects against acute ethanol-induced hepatic injury in mice. GC-MS analysis revealed that unsaturated fatty acids (UFAs) account for 83.76% of the total fatty acids; in particular, the linoleic acid (C18:2) is the predominant polyunsaturated fatty acid (PUFA), and the compounds of squalene and six phytosterols (or phytostanols) were identified in unsaponifiable matter of FMBO. The antioxidant activity examination of FMBO in vitro showed highly ferric-reducing antioxidant power and scavenging effects against DPPH· and HO· radicals. Furthermore, the protective effect of FMBO against acute hepatic injuries induced by ethanol was verified in mice. In this, intragastric administration with different dosages of FMBO in mice ahead of acute ethanol administration could observably antagonize the ethanol-induced increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and the hepatic malondialdehyde (MDA) levels, respectively, along with enhanced hepatic superoxide dismutase (SOD) levels relative to the control. Hepatic histological changes were also observed and confirmed that FMBO is capable of attenuating ethanol-induced hepatic injury. PMID:24909671

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

    Microsoft Academic Search

    Leandro P Moura; Guilherme M Puga; Wladimir R Beck; Inaian P Teixeira; Carolina Ana Ghezzi; Gláucio A Silva; Maria Alice R Mello

    2011-01-01

    Background  Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue\\u000a accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD).\\u000a \\u000a \\u000a \\u000a \\u000a 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.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Diabetes was induced in the

  13. IL-22 modulates gut epithelial and immune barrier functions following acute alcohol exposure and burn injury

    PubMed Central

    Rendon, Juan L.; Li, Xiaoling; Akhtar, Suhail; Choudhry, Mashkoor A.

    2012-01-01

    Interleukin (IL)–22 maintains gut epithelial integrity and expression of antimicrobial peptides (AMPs) Reg3? and Reg3?. Our laboratory has shown that acute alcohol/ethanol (EtOH) exposure prior to burn injury results in increased gut permeability, intestinal T cell suppression and enhanced bacterial translocation. Herein, we determined the effect of combined EtOH intoxication and burn injury on intestinal levels of IL-22 as well as Reg3? and Reg3? expression. We further examined whether in vivo restitution of IL-22 restores gut permeability, Reg3? and Reg3? levels, and bacterial load (e.g. gut bacterial growth) within the intestine following EtOH and burn injury. Male mice, ~25g, were gavaged with EtOH (2.9 mg/kg) prior to receiving a ~12.5% total body surface area full thickness burn. Mice were immediately treated with saline control or IL-22 (1 mg/kg) by i.p. injection. One day post injury, there was a significant decrease in intestinal IL-22, Reg3? and Reg3? expression along with an increase in intestinal permeability and gut bacterial load following EtOH combined with burn injury, as compared to sham injury. Treatment with IL-22 normalized Reg3? and Reg3? expression, and attenuated the increase in intestinal permeability following EtOH and burn injury. Qualitatively, IL-22 treatment reduced the bacterial load in nearly half of mice receiving EtOH combined with burn injury. Our data indicate that IL-22 maintains gut epithelial and immune barrier integrity following EtOH and burn injury; thus, the IL-22/AMP pathway may provide a therapeutic target for the treatment of patients who sustain burn injury under the influence of EtOH. PMID:23143063

  14. HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis

    PubMed Central

    1993-01-01

    We have recently developed the technology to identify and characterize the human histocompatibility leukocyte antigen (HLA) class I- restricted, CD8+ cytotoxic T lymphocyte (CTL) response to hepatitis B virus (HBV)-encoded antigens in patients with acute viral hepatitis. CTL are expanded in vitro by stimulation with HBV-derived synthetic peptides and selected by restimulation with a panel of HLA-matched stable transfectants that express the corresponding HBV protein. We have recently reported the existence of an HLA-A2-restricted, CD8+ CTL response to an epitope located between residues 18 and 27 of the HBV nucleocapsid core antigen (HBcAg). We now report the discovery of a CTL epitope located between HBcAg residues 141 and 151 that completely overlaps a critical domain in the viral nucleocapsid protein that is essential for its nuclear localization and genome packaging functions as well as processing of the precore protein. The CTL response to this epitope is dually restricted by the HLA-A31 and HLA-Aw68 alleles, which, unexpectedly, appear to use a common binding motif based on the results of alanine substitution and competition analysis, and the binding properties of these two alleles predicted from their known primary sequence, and from the three-dimensional structure of HLA-Aw68. We have also demonstrated that the HBV-specific CTL response to this epitope is polyclonal during acute viral hepatitis, since these two restriction elements can present the HBcAg 141-151 epitope to independent CTL clones derived from a single patient; and that the CTL response is multispecific, since HLA-A2-restricted and HLA-Aw68- restricted CTL responses to HBcAg 18-27 and HBcAg 141-151, respectively, have been identified to coexist in another patient. The foregoing argue against the emergence of CTL escape mutants as a significant problem during HBV infection, especially at this locus, where mutations might be incompatible with viral replication. Finally, our data suggest an association between the HBV-specific CTL response and viral clearance, and they have implications for the design of immunotherapeutic strategies to terminate HBV infection in chronically infected patients. PMID:7679709

  15. 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

  16. Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection

    PubMed Central

    Zekri, Abdel-Rahman N; Hafez, Mohamed M; Mohamed, Nahed I; Hassan, Zeinab K; El-Sayed, Manal H; Khaled, Mohsen M; Mansour, Tarek

    2007-01-01

    Background There are eight genotypes of hepatitis B virus (A-H) and subgenotypes are recognized. Genotyping can be accomplished based on a partial sequence of HBV genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping. This study was undertaken to determine the HBV genotypes in Egyptian pediatric cancer patients with acute and chronic liver disease. Methods HBV genotypes were determined in 22 patients who had acute forms of liver disease (AH) and in 48 patients with chronic active hepatitis (CAH). A type-specific primer based the nested-PCR method was employed in the HBV genotyping. Results This study showed that HBV infections in pediatric cancer patients are attributed predominantly to viral genotypes D and B that constituted 37.1% and 25.7%, respectively of the total infections. In addition, there was a relatively high prevalence of mixed infections of 15.7% among the studied group especially mixed A/D genotype infections. Genotype D was found significantly more often in patients with CAH than in patients with AH [23/48(47.9%) v 3/22 (13.6%)]. Conclusion These findings show the distribution of HBV A-D genotypes in pediatric cancer Egyptian patients. Furthermore, our results indicate a markedly high prevalence of mixed A/D genotype infections in subjects with CAH and a possible association of mixed infections with the severity of liver diseases. PMID:17631684

  17. Sleep Architecture in Adolescent Marijuana and Alcohol Users during Acute and Extended Abstinence

    PubMed Central

    Cohen-Zion, Mairav; Drummond, Sean P.A.; Padula, Claudia B.; Winward, Jennifer; Kanady, Jennifer; Medina, Krista L.; Tapert, Susan F.

    2009-01-01

    This study examined sleep changes following cessation of marijuana and alcohol use during late adolescence. Twenty-nine heavy marijuana and alcohol users and 20 matched controls were studied during a 28-day monitored abstinence period. Sleep as examined as a function of prior substance use during Nights 1–2 and Nights 27–28. On Night 2, percent Rapid Eye Movement sleep was predicted by past month alcohol use, whereas percent Slow Wave Sleep was predicted by marijuana intake. By Night 28, neither alcohol no marijuana use predicted any sleep architecture measure. However, on Night 28, indices of period limb movements (PLMs) in sleep were predicted by marijuana and alcohol intake. Results indicate that in adolescents: (1) cessation of heavy marijuana and alcohol use may influence sleep; (2) most sleep abnormalities abate within several weeks of abstinence; and (3) PLMs may increase following abstinence. PMID:19505769

  18. Subjective effects and changes in steroid hormone concentrations in humans following acute consumption of alcohol

    Microsoft Academic Search

    Amira Pierucci-Lagha; Jonathan Covault; Richard Feinn; Rahul T. Khisti; Christine E. Marx; Lawrence J. Shampine; Henry R. Kranzler

    2006-01-01

    Background:\\u000a   GABAA receptors are an important site of action of endogenous neurosteroids and an important mediator of several behavioral effects of alcohol. This study examined the effects of alcohol on plasma steroid hormone concentrations on the hypothesis that the endocrine effects mediate some of the subjective effects of alcohol.\\u000a Methods:\\u000a   Thirty-two healthy subjects (17 men) with no history of a

  19. Acute recovery and tolerance to low doses of alcohol: Differences in cognitive and motor skill performance

    Microsoft Academic Search

    M. D. Vogel-Sprott

    1979-01-01

    Two groups of male social drinkers were trained on a coding and pursuit rotor (PR) task, and then were tested on these two tasks under either alcohol (0.88 ml 94.6% alcohol\\/kg) or placebo. These treatments were repeated four times at weekly intervals, with similar blood alcohol concentrations (BAC, P>0.50) attained on all sessions (mean peak=0.082%). Drug-free coding and PR, tested

  20. Khat (Catha Edulis) as a possible cause of autoimmune hepatitis

    PubMed Central

    Riyaz, Shahzad; Imran, Mohammad; Gleeson, Dermot; Karajeh, Mohammed A

    2014-01-01

    AIM: To investigate the potential role of khat in triggering auto immune hepatitis. METHODS: Patients with a history of khat use and acute hepatitis were identified using the computer database in the hepatology department at the Royal Hallamshire Hospital. They were then assessed for probability of having autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria. RESULTS: Six patients were identified. All of them had presented with acute hepatitis on a background of khat. All were male and five of these patients were of Somali origin, while one patient was from Yemen. The patients were given points on the modified autoimmune hepatitis score which is based on their liver enzymes, autoimmune screen, exclusion of viral hepatitis alcohol and drugs, immunoglobulin levels and liver histology. The patients were given a score of -4 for khat use due to its potential to cause drug induced liver injury. Five of these patients scored between 10 and 15 points, placing them in the probable group for having autoimmune hepatitis. All of these patients were treated with prednisolone and demonstrated a good response to immunosuppression. CONCLUSION: One possibile cause of hepatotoxicity with khat could be via triggering of autoimmune hepatitis in a genetically susceptible individual. Further studies are needed for confirmation. PMID:24672645

  1. The Acute Effects of Alcohol on Sleep Architecture in Late Adolescence

    PubMed Central

    Chan, Julia K. M.; Trinder, John; Andrewes, Holly E.; Colrain, Ian M.; Nicholas, Christian L.

    2013-01-01

    Background Alcohol consumption is prevalent in late adolescence, however little is known about its effect on sleep in this group. In mature adults, alcohol decreases sleep onset latency (SOL) and sleep efficiency (SE) and increases wake after sleep onset (WASO). It also increases slow wave sleep (SWS) and decreases REM sleep in the first half of the night, with the inverse occurring in the second half. Alcohol’s effect on sleep during late adolescence is of interest given that this age group shows both dramatic increases in alcohol consumption, and significant developmental changes in the central nervous system. This study examined the effect of alcohol on sleep architecture in women and men aged 18–21 years and whether previously reported sleep architecture effects may have been as an artificial result of changes to sleep cycle length. Methods 24 (12 female) healthy 18–21 year old light social drinkers (19.1±1.0yrs) underwent two conditions: pre-sleep alcohol (Target BAC 0.10%) and placebo administered under controlled conditions, followed by standard polysomnography. Results In the alcohol condition, mean breath alcohol concentration (BAC) at lights out was 0.084 ±0.016%. Time in bed, total sleep time and sleep onset latency (all p>.05) did not differ between conditions. However, there was less REM (p=.011) and more stage 2 sleep (p=.035) in the alcohol condition. Further, alcohol increased SWS (p=.02) and decreased REM sleep (p<.001) in the first half of the night and disrupted sleep in the second half, with increased WASO (interaction: p=.034), and decreased SE (p=.04) and SWS (p=.01) and no REM sleep rebound in the second half of the night (p=.262). Additionally, alcohol had no effect on sleep cycle length (p=.598). Conclusions The results were broadly consistent with the adult literature with the novel extension that half night sleep architecture effects could not be attributed to changes in sleep cycle length. However, alcohol did not reduce SOL, or result in a REM rebound following reduced REM in the first half of the night. The results suggest that the effects of alcohol on sleep are modified by sleep’s prevailing developmental stage. PMID:23800287

  2. Tissue Localization of Australia Antigen Immune Complexes in Acute and Chronic Hepatitis and Liver Cirrhosis

    PubMed Central

    Nowos?awski, Adam; Krawczy?ski, Krzysztof; Brzosko, Witold J.; Madali?ski, Kazimierz

    1972-01-01

    In a significant percentage of examined cases of fulminant hepatitis, subacute hepatitis, chronic aggressive hepatitis, liver cirrhosis and chronic persistent hepatitis, Australia (hepatitis-associated) antigen (Au HAA) was identified in the liver and in extrahepatic locations. The several immunofluorescent patterns of Au HAA localization in hepatocytes strongly suggested various stages of Au HAA accumulation and release. Deposits of a mixture of immunoglobulins G and M and occasionally ?1C-globulin were found in the cytoplasm of Au HAA containing hepatocytes, on their plasma membranes, on or in the nuclei, in the cytoplasm of Kupffer cells and, rarely, in the sinusoids. The accompanying tissue changes were hepatocellular degeneration and necrosis. These intra- and extracellular complexes of Au HAA and immunoglobulins displayed strong affinity for guinea pig complement in the immunohistochemical complement fixation reaction. When tested by immunodiffusion in agar, IgG dissociated from these complexes by potassium thiocyanate (KSCN) treatment showed anti-Au HAA specificity. In fulminant hepatitis neither Au HAA nor immunoglobulins and complement were found in the liver. In chronic aggressive hepatitis and subacute hepatitis the amount of the Au HAA immune complexes identified in the liver was approximately inversely proportional to the extent and severity of the parenchymal lesions. In liver cirrhosis and chronic persistent hepatitis there was a positive correlation between the amount of the Au HAA immune complexes found in the liver and the degree of hepatocellular damage. The deposits of Au HAA, identified in extrahepatic locations including germinal centers of lymph nodes and spleen, kidney glomeruli and blood vessel walls, were as a rule accompanied by deposits of IgG, IgM, ?1C-globulin and fibrin. All these deposits showed strong affinity for guinea pig complement in the immunohistochemical reaction of complement fixation. Germinal center activation, chronic membraneous glomerulonephritis, panarteritis and simple arteriolar hyalinosis were found at sites of localization of these deposits. ImagesFig 21Fig 22Fig 23Fig 24Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 25Fig 26Fig 27Fig 28Fig 29Fig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14Fig 15Fig 16Fig 17Fig 18Fig 19Fig 20 PMID:4628111

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

    PubMed Central

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

    2014-01-01

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

  4. Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients.

    PubMed

    Nevot, M; Boesecke, C; Parera, M; Andrés, C; Franco, S; Revollo, B; Ingiliz, P; Tural, C; Clotet, B; Rockstroh, J K; Martinez, M A

    2014-06-01

    The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously cleared HCV, although 78% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV-coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV-1-positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment. PMID:24674023

  5. Hepatitis B immunoglobulins inhibit dendritic cells and T cells and protect against acute rejection after liver transplantation.

    PubMed

    Kwekkeboom, J; Tha-In, T; Tra, W M W; Hop, W; Boor, P P C; Mancham, S; Zondervan, P E; Vossen, A C T M; Kusters, J G; de Man, R A; Metselaar, H J

    2005-10-01

    The efficacy of anti-viral intravenous immunogobulins (anti-HBs Ig and anti-CMV Ig) in preventing acute rejection after liver transplantation was assessed in a retrospective analysis, and correlated to their effects on immune cells in vitro. HBs Ag-positive liver graft recipients (n = 40) treated prophylactically with anti-HBs Ig had a significantly lower incidence of acute rejection compared with recipients without viral hepatitis (n = 147) (12% vs. 34%; p = 0.012), while the incidence of rejection in HCV-positive recipients (n = 29) was similar to that in the control group. Treatment with anti-CMV Ig (n = 18) did not protect against rejection. In vitro, anti-HBs Ig suppressed functional maturation of and cytokine production by human blood-derived dendritic cells (DC) at concentrations similar to the serum concentrations reached during anti-HBs Ig treatment of liver graft recipients. In addition, anti-HBs Ig inhibited allo-antigen- and lectin-stimulated proliferation of peripheral T cells. Anti-CMV Ig suppressed functional DC-maturation and alloantigen-stimulated T-cell proliferation, but not lectin-driven T-cell proliferation. In conclusion, anti-HBs Ig protects against acute rejection after liver transplantation, probably by functional inhibition of the two principal immune cells involved in allograft rejection, DC and T cells. PMID:16162187

  6. Effect of allyl alcohol on hepatic transporter expression: Zonal patterns of expression and role of Kupffer cell function

    PubMed Central

    Campion, Sarah N.; Tatis-Rios, Cristina; Augustine, Lisa M.; Goedken, Michael J.; van Rooijen, Nico; Cherrington, Nathan J.; Manautou, José E.

    2015-01-01

    During APAP toxicity, activation of Kupffer cells is critical for protection from hepatotoxicity and up-regulation of multidrug resistance-associated protein 4 (Mrp4) in centrilobular hepatocytes. The present study was performed to determine the expression profile of uptake and efflux transporters in mouse liver following treatment with allyl alcohol (AlOH), a periportal hepatotoxicant. This study also investigated the role of Kupffer cells in AlOH hepatotoxicity, and whether changes in transport protein expression by AlOH are dependent on the presence of Kupffer cells. C57BL/6J mice received 0.1 ml clodronate liposomes to deplete Kupffer cells or empty liposomes 48 h prior to dosing with 60 mg/kg AlOH, i.p. Hepatotoxicity was assessed by plasma ALT and histopathology. Hepatic transporter mRNA and protein expression were determined by branched DNA signal amplification assay and Western blotting, respectively. Depletion of Kupffer cells by liposomal clodronate treatment resulted in heightened susceptibility to AlOH toxicity. Exposure to AlOH increased mRNA levels of several Mrp genes, while decreasing organic anion transporting polypeptides (Oatps) mRNA expression. Protein analysis mirrored many of these mRNA changes. The presence of Kupffer cells was not required for the observed changes in uptake and efflux transporters induced by AlOH. Immunofluorescent analysis revealed enhanced Mrp4 staining exclusively in centrilobular hepatocytes of AlOH treated mice. These findings demonstrate that Kupffer cells are protective from AlOH toxicity and that induction of Mrp4 occurs in liver regions away from areas of AlOH damage independent of Kupffer cell function. These results suggest that Kupffer cell mediators do not play a role in mediating centrilobular Mrp4 induction in response to periportal damage by AlOH. PMID:19371622

  7. Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B.

    PubMed

    Lee, Jong Ho; Hong, Sun Pyo; Jang, Eun Sun; Park, Sang Jong; Hwang, Seong Gyu; Kang, Sook-Kyoung; Jeong, Sook-Hyang

    2015-06-01

    Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations. J. Med. Virol. 87:993-998, 2015. © 2015 Wiley Periodicals, Inc. PMID:25712861

  8. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    PubMed Central

    Pan, Si-Yuan; Yu, Zhi-Ling; Dong, Hang; Xiang, Chun-Jing; Fong, Wang-Fun; Ko, Kam-Ming

    2011-01-01

    Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5?g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1?g/kg/day for 7 days, i.g.) significantly lowered the hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46?g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment. PMID:19592476

  9. Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

    PubMed Central

    Richey, Laura; Doremus-Fitzwater, Tamara L.; Buck, Hollin M.; Deak, Terrence

    2012-01-01

    Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100 ?g/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5 g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed. PMID:22921768

  10. Susceptibility to acetaminophen (APAP) toxicity unexpectedly is decreased during acute viral hepatitis in mice

    Microsoft Academic Search

    Yonas Getachew; Laura James; William M. Lee; Dwain L. Thiele; Bonnie C. Miller

    2010-01-01

    Acetaminophen (APAP) hepatotoxicity results from cytochrome P450 metabolism of APAP to the toxic metabolite, n-acetyl-benzoquinone imine (NAPQI), which reacts with cysteinyl residues to form APAP adducts and initiates cell injury. As APAP is commonly used during viral illnesses there has been concern that APAP injury may be additive to that of viral hepatitis, leading physicians to advise against its use

  11. DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection

    Microsoft Academic Search

    CATHERINE B. BIGGER; KATHLEEN M. BRASKY; ROBERT E. LANFORD

    2001-01-01

    Hepatitis C virus (HCV) poses a worldwide health problem in that the majority of individuals exposed to HCV become chronically infected and are predisposed for developing significant liver disease. DNA microarray technology provides an opportunity to survey transcription modulation in the context of an infectious disease and is a particularly attractive approach in characterizing HCV-host interactions, since the mechanisms underlying

  12. Intrinsic aerobic capacity impacts susceptibility to acute high-fat diet-induced hepatic steatosis.

    PubMed

    Morris, E Matthew; Jackman, Matthew R; Johnson, Ginger C; Liu, Tzu-Wen; Lopez, Jordan L; Kearney, Monica L; Fletcher, Justin A; Meers, Grace M E; Koch, Lauren G; Britton, Stephen L; Rector, R Scott; Ibdah, Jamal A; MacLean, Paul S; Thyfault, John P

    2014-08-15

    Aerobic capacity/fitness significantly impacts susceptibility for fatty liver and diabetes, but the mechanisms remain unknown. Herein, we utilized rats selectively bred for high (HCR) and low (LCR) intrinsic aerobic capacity to examine the mechanisms by which aerobic capacity impacts metabolic vulnerability for fatty liver following a 3-day high-fat diet (HFD). Indirect calorimetry assessment of energy metabolism combined with radiolabeled dietary food was employed to examine systemic metabolism in combination with ex vivo measurements of hepatic lipid oxidation. The LCR, but not HCR, displayed increased hepatic lipid accumulation in response to the HFD despite both groups increasing energy intake. However, LCR rats had a greater increase in energy intake and demonstrated greater daily weight gain and percent body fat due to HFD compared with HCR. Additionally, total energy expenditure was higher in the larger LCR. However, controlling for the difference in body weight, the LCR has lower resting energy expenditure compared with HCR. Importantly, respiratory quotient was significantly higher during the HFD in the LCR compared with HCR, suggesting reduced whole body lipid utilization in the LCR. This was confirmed by the observed lower whole body dietary fatty acid oxidation in LCR compared with HCR. Furthermore, LCR liver homogenate and isolated mitochondria showed lower complete fatty acid oxidation compared with HCR. We conclude that rats bred for low intrinsic aerobic capacity show greater susceptibility for dietary-induced hepatic steatosis, which is associated with a lower energy expenditure and reduced whole body and hepatic mitochondrial lipid oxidation. PMID:24961240

  13. Incubation Phase of Acute Hepatitis B in Man: Dynamic of Cellular Immune Mechanisms

    Microsoft Academic Search

    George J. M. Webster; Stephanie Reignat; Mala K. Maini; Simon A. Whalley; Graham S. Ogg; Abigail King; David Brown; Peter L. Amlot; Roger Williams; Diego Vergani; Geoffrey M. Dusheiko; Antonio Bertoletti

    2000-01-01

    After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection,

  14. Risk factors for acute hepatitis A infection in Korea in 2007 and 2009: a case-control study.

    PubMed

    Seo, Joo Youn; Choi, Bo Youl; Ki, Moran; Jang, Hye Lim; Park, Hee Suk; Son, Hyun Jin; Bae, Si Hyun; Kang, Jin Han; Jun, Dae Won; Lee, Jin-Woo; Hong, Young Jin; Kim, Young Seok; Kim, Chang-Hwi; Chang, U Im; Kim, Jong-Hyun; Yang, Hyeon Woong; Kim, Hong Soo; Park, Kyeong Bae; Hwang, Jae Seok; Heo, Jeong; Kim, In Hee; Kim, Jung Soo; Cheon, Gab Jin

    2013-06-01

    This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas. PMID:23772157

  15. Xenobiotic Metabolism: The Effect of Acute Kidney Injury on Non-Renal Drug Clearance and Hepatic Drug Metabolism

    PubMed Central

    Dixon, John; Lane, Katie; MacPhee, Iain; Philips, Barbara

    2014-01-01

    Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth. PMID:24531139

  16. Severe Aplastic Anemia following Acute Hepatitis from Toxic Liver Injury: Literature Review and Case Report of a Successful Outcome

    PubMed Central

    Qureshi, Kamran; Sarwar, Usman; Khallafi, Hicham

    2014-01-01

    Hepatitis associated aplastic anemia (HAAA) is a rare syndrome in which severe aplastic anemia (SAA) complicates the recovery of acute hepatitis (AH). HAAA is described to occur with AH caused by viral infections and also with idiopathic cases of AH and no clear etiology of liver injury. Clinically, AH can be mild to fulminant and transient to persistent and precedes the onset SAA. It is assumed that immunologic dysregulation following AH leads to the development of SAA. Several observations have been made to elucidate the immune mediated injury mechanisms, ensuing from liver injury and progressing to trigger bone marrow failure with the involvement of activated lymphocytes and severe T-cell imbalance. HAAA has a very poor outcome and often requires bone marrow transplant (BMT). The findings of immune related myeloid injury implied the use of immunosuppressive therapy (IST) and led to improved survival from HAAA. We report a case of young male who presented with AH resulting from the intake of muscle building protein supplements and anabolic steroids. The liver injury slowly resolved with supportive care and after 4 months of attack of AH, he developed SAA. He was treated with IST with successful outcome without the need for a BMT. PMID:25587471

  17. Low rate of sustained virological response in an outbreak of acute hepatitis C in HIV-infected patients.

    PubMed

    Laguno, Montserrat; Martínez-Rebollar, Maria; Perez, Iñaki; Costa, Josep; Larrousse, Maria; Calvo, Marta; Loncá, Montse; Muñoz, Ana; González-Cordón, Ana; Blanco, José Luís; Martínez, Esteban; Gatell, Josep Maria; Mallolas, Josep

    2012-10-01

    Recent reports have suggested an increased risk of acute hepatitis C (AHC) infection in homosexual HIV-infected men and that early treatment with interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution. A retrospective analysis of 38 HIV-infected patients who were consecutively diagnosed as developing AHC, defined by both seroconversion of anti-hepatitis C virus (HCV) antibodies and detection of serum HCV-RNA in those with previous negative results. Thirty-six patients were men with history of unprotected sexual intercourse with men and two were women with sexual and nosocomial risk factors. AHC infection was asymptomatic in 26 patients; asthenia and jaundice were the most frequent symptoms. HCV genotype 1 was present in 19 patients and genotype 4 in 14 patients. Thirty-five patients received early antiviral treatment with pegylated interferon-alfa associated with ribavirin; 15 of the 32 patients who completed the follow-up (47%) achieved a sustained virological response, as defined by undetectable HCV-RNA 6 months after the end of therapy. There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men. In our experience, early treatment of AHC with pegylated interferon-alfa plus ribavirin in HIV patients achieves poor results. PMID:22428909

  18. 5-Aminoimidazole-4-carboxamide-1-?-d-ribofuranoside alleviated carbon tetrachloride-induced acute hepatitis in mice.

    PubMed

    Yang, Changming; Gong, Xianqiong; Ai, Qing; Ge, Pu; Lin, Ling; Zhang, Li

    2015-04-01

    AMP-activated protein kinase (AMPK) is one of the principal cellular energy sensors participating in maintenance of energy balance but recent evidences also suggested that AMPK might be involved in the regulation of inflammation. In the present study, the AMPK activator 5-aminoimidazole-4-carboxamide-1-?-d-ribofuranoside (AICAR) was used to investigate the potential roles of AMPK in carbon tetrachloride (CCl4)-induced acute hepatitis. The experimental data indicated that treatment with AICAR significantly decreased the elevation of plasma aminotransferases and alleviated hepatic histological abnormalities in CCl4-exposed mice. Treatment with AICAR also inhibited the increase of myeloperoxidase (MPO), the induction of TNF-?, IL-6, inducible nitric oxide synthase (iNOS), nitric oxide and the upregulation of matrix metalloproteinase 2 (MMP-2), MMP-3 and MMP-9 in mice exposed to CCl4. These effects were associated with suppressed nuclear accumulation of NF-?B p65. These results indicated that the AMPK activator AICAR effectively suppressed the inflammatory responses and alleviated liver damage induced by CCl4, implying that AMPK activation might be beneficial for ameliorating inflammation-based liver damage. PMID:25711693

  19. Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication.

    PubMed

    Blednov, Y A; Benavidez, J M; Black, M; Chandra, D; Homanics, G E; Rudolph, U; Harris, R A

    2013-04-01

    GABA type A receptors (GABA(A)-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABA(A)-R subunits (?1, ?2, ?3, ?4, ?5 and ?). Only mice lacking the ?2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the ?2-subunit (Blednov et al., 2011). All together, they indicate that aversive property of ethanol is dependent on ethanol action on ?2-containing GABA(A)-R. Deletion of the ?2-subunit led to faster recovery whereas absence of the ?3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the ?2 and ?3 null mutants were found for flurazepam motor incoordination. However, no differences in recovery were found in motor-incoordinating effects of an ?1-selective modulator (zolpidem) or an ?4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABA(A)-R subunits: ?2 and ?3. For motor activity, ?3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both ?2 (-/-) and ?3 (-/Y) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing ?2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the ?2 subunit with human alcoholism. PMID:23147414

  20. Rhabdomyolysis due to Lamivudine administration in acute viral hepatitis B infection: a case report from Malaysia

    PubMed Central

    Baharin, Janudin; Sahari, Narisa Sulaiman; Lim, Sazlyna Mohd Sazlly

    2014-01-01

    Rhabdomyolysis is a serious but rare side effect of Lamivudine treatment. Therefore, appropriate biochemical monitoring should be undertaken when it is used in the treatment of hepatitis B. This paper presents a case of Lamivudine-associated rhabdomyolysis in a 31-year-old man with congenital heart disease and hepatitis B. Three days after starting Lamivudine, the patient developed myalgia. Significant muscle tenderness and swelling of the upper and lower limbs was discovered during a physical examination. Creatine kinase was markedly raised. Lamivudine-induced rhabdomyolysis was suspected and the drug was discontinued. Symptoms and creatine kinase activity improved within four days of Lamivudine cessation and hydration. Early identification of Lamivudine-induced rhabdomyolysis is key in preventing this potentially fatal drug reaction; withdrawal of Lamivudine may contribute to complete remission of rhabdomyolysis.

  1. Effects of acute doxorubicin treatment on hepatic proteome lysine acetylation status and the apoptotic environment

    PubMed Central

    Dirks-Naylor, Amie J; Kouzi, Samir A; Bero, Joseph D; Tran, Ngan TK; Yang, Sendra; Mabolo, Raean

    2014-01-01

    AIM: To determine if doxorubicin (Dox) alters hepatic proteome acetylation status and if acetylation status was associated with an apoptotic environment. METHODS: Doxorubicin (20 mg/kg; Sigma, Saint Louis, MO; n = 8) or NaCl (0.9%; n = 7) was administered as an intraperitoneal injection to male F344 rats, 6-wk of age. Once animals were treated with Dox or saline, all animals were fasted until sacrifice 24 h later. RESULTS: Dox treatment decreased proteome lysine acetylation likely due to a decrease in histone acetyltransferase activity. Proteome deacetylation may likely not be associated with a proapoptotic environment. Dox did not increase caspase-9, -8, or -3 activation nor poly (adenosine diphosphate-ribose) polymerase-1 cleavage. Dox did stimulate caspase-12 activation, however, it likely did not play a role in apoptosis induction. CONCLUSION: Early effects of Dox involve hepatic proteome lysine deacetylation and caspase-12 activation under these experimental conditions. PMID:25225604

  2. Chronic Hepatitis C Virus Infection is Associated with All-Cause and Liver-Related Mortality in a Cohort of HIV-Infected Patients with Alcohol Problems

    PubMed Central

    Fuster, Daniel; Cheng, Debbie M.; Quinn, Emily K.; Nunes, David; Saitz, Richard; Samet, Jeffrey H.; Tsui, Judith I.

    2013-01-01

    Aims To assess the association between hepatitis C virus (HCV) infection and overall and liver-related death in human immunodeficiency virus (HIV)-infected patients with alcohol problems. Design We analyzed data from a cohort of HIV-infected adults with current or past alcohol problems enrolled between 2001 and 2003, searching for causes of death until 2010 using the National Death Index. Setting and participants Participants were HIV-infected adults with current or past alcohol problems, recruited in Boston, MA from HIV clinics at two hospitals, homeless shelters, drug treatment programs, subject referrals, flyers, and another cohort study with comparable recruitment sites. Measurements The primary and secondary outcomes were all-cause and liver-related mortality, respectively. The main independent variable was HCV RNA status (positive vs. negative). Mortality rates and Kaplan-Meier survival curves were calculated by HCV status for both overall and liver-related mortality. Cox proportional hazards models were used to assess the association between HCV infection and overall and liver-related death, adjusting for alcohol and drug use over time. Findings 397 adults (50% HCV-infected) were included. As of December 31, 2009, 83 cohort participants had died (60 HCV-infected, 23 HCV-uninfected; log rank test p<0.001), and 26 of those deaths were liver-related (21 HCV-infected, 5 HCV-uninfected; log rank test p<0.001). All-cause and liver-related mortality rates were 4.68 and 1.64 deaths per 100 person-years for HCV-infected patients and 1.65 and 0.36 per 100 person-years for those without HCV, respectively. In the fully adjusted Cox model, HCV infection was associated with both overall [HR 2.55 (95%CI:1.50–4.33), p<0.01], and liver-related mortality [HR 3.24 (95%CI:1.18–8.94), p=0.02]. Conclusion Hepatitis C virus infection is independently associated with all-cause and liver-related mortality in human immunodeficiency virus-infected patients with alcohol problems, even when accounting for alcohol and other drug use. PMID:24112091

  3. Successful antiviral triple therapy in a longstanding refractory hepatitis C virus infection with an acute kidney injury.

    PubMed

    Callau Monje, David; Braun, Niko; Latus, Joerg; Amann, Kerstin; Alscher, Mark Dominik; Kimmel, Martin

    2014-01-01

    Introduction. The HCV infection is a common disease with many chronically infected patients worldwide. So far, the standard therapy of a chronic HCV infection consisted of interferon as single therapy or in combination with ribavirin. After approval of the two protease inhibitors, boceprevir and telaprevir, the standard therapy for patients with genotype 1 changed. In patients with acute kidney injury (AKI) these therapies are not approved and have so far not been evaluated in studies. Case Report. In April 2012, a 58-year-old female was admitted due to a cryoglobulin-positive chronic HCV infection which had been treated with interferon and ribavirin. Currently, the patient was admitted because of severe complications with an acute kidney injury. We treated our patient successfully with a boceprevir based triple therapy. Conclusion. Limited data suggests that a therapy with ribavirin in patients with AKI seems to be safe under close monitoring. Our patient was treated successfully with a protease inhibitor based triple therapy. Nevertheless, it is necessary to plan an interventional study to evaluate the exact risk-benefit profile of triple therapy regimens in patients with AKI and hepatitis C. PMID:25197586

  4. Upregulation of heat shock protein 32 with hemin alleviates acute heat-induced hepatic injury in mice.

    PubMed

    Li, Cheng-Min; Li, Lian; Wu, Jie; Bai, Jing-Yan; Sun, Yu; Huang, Shuai; Wang, Gen-Lin

    2014-09-01

    Heat shock protein 32 (HSP32) is a stress response protein that can be induced by heat stress in the liver, and its induction can act as an important cellular defence mechanism against heat-induced liver injury. To investigate the functional role of HSP32 in protecting liver tissue against heat stress in mice and the mechanism by which it achieves this protective effect, HSP32 expression and carbon monoxide (CO) contents in a model of mice subjected to acute, transient heat exposure were examined. Furthermore, functional and histological parameters of liver damage and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions and caspase-3 expression were also investigated in this study. We found that heat treatment of mice produced severe hepatic injury, whereas upregulation of HSP32 with hemin pretreatment prevented mice from liver damage. In contrast, addition of Sn-protoporphyrin (SnPP) to inhibit HSP32 expression completely reversed its hepatoprotective effect. It is concluded that upregulation of HSP32 by hemin could alleviate acute heat-induced hepatocellular damage in mice, and its by-product CO seems to play a more important role in hepatoprotective mechanism. PMID:24473736

  5. Successful Antiviral Triple Therapy in a Longstanding Refractory Hepatitis C Virus Infection with an Acute Kidney Injury

    PubMed Central

    Braun, Niko; Latus, Joerg; Amann, Kerstin; Alscher, Mark Dominik; Kimmel, Martin

    2014-01-01

    Introduction. The HCV infection is a common disease with many chronically infected patients worldwide. So far, the standard therapy of a chronic HCV infection consisted of interferon as single therapy or in combination with ribavirin. After approval of the two protease inhibitors, boceprevir and telaprevir, the standard therapy for patients with genotype 1 changed. In patients with acute kidney injury (AKI) these therapies are not approved and have so far not been evaluated in studies. Case Report. In April 2012, a 58-year-old female was admitted due to a cryoglobulin-positive chronic HCV infection which had been treated with interferon and ribavirin. Currently, the patient was admitted because of severe complications with an acute kidney injury. We treated our patient successfully with a boceprevir based triple therapy. Conclusion. Limited data suggests that a therapy with ribavirin in patients with AKI seems to be safe under close monitoring. Our patient was treated successfully with a protease inhibitor based triple therapy. Nevertheless, it is necessary to plan an interventional study to evaluate the exact risk-benefit profile of triple therapy regimens in patients with AKI and hepatitis C. PMID:25197586

  6. Effect of Allyl Alcohol-induced Sublethal Hepatic Damage upon Doxorubicin Metabolism and Toxicity in the Rabbit1

    Microsoft Academic Search

    Dean E. Brenner; Lowell B. Anthony; Susan Halter; N. Lindsay Harris; Jerry C. Collins; Kenneth R. HÃ

    A model of hepatic dysfunction in vivo has been developed in rabbits to determine the effects of sublethal hepatocellular necrosis upon doxo- rubicin pharmacology. Eight New Zealand white rabbits were given 3 mg\\/kg doxorubicin i.v. Plasma doxorubicin and metabolite pharmacoki- netics were determined and toxicity assessed by nadir complete blood counts. Hepatic function was assessed by the pulmonary excretion rate

  7. Caffeine protects against alcohol-induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells.

    PubMed

    Wang, Qi; Dai, Xuefei; Yang, Wanzhi; Wang, He; Zhao, Han; Yang, Feng; Yang, Yan; Li, Jun; Lv, Xiongwen

    2015-04-01

    Alcoholic liver fibrosis (ALF) is characterized by hyperplasia of extracellular matrix under long-term alcohol stimulation. Hepatic stellate cell (HSC) activation plays an important role in promoting hepatic fibrogenesis. Caffeine, as the main active component of coffee and tea, was widely consumed in daily life. It was always a thought that caffeine can reduce the probability of suffering from liver diseases. In this study, we attempt to validate the hypothesis that caffeine inhibits activation of HSCs which were isolated from rat ALF model. The rats were gavaged by ethanol to establish ALF model and then treated with different concentrations of caffeine or colchicine. Serum was collected to measure the contents of serum alanine aminotransferase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), laminin (LN), N-terminal peptide of type III procollagen (PIIINP) and type IV collagen (CIV). Then liver tissues were obtained for hematoxylin-eosin staining and Sirius-red staining. Others were treated through liver perfusion to isolate primary rat HSCs. Interestingly, we found that caffeine significantly decreased ALT, AST, HA, LN, PIIINP and CIV levels and reversed liver fibrosis in rat ALF models. Results of immunohistochemistry, real-time PCR and western blot indicated that caffeine could reduce fibrosis and inhibit cAMP/PKA/CREB signal pathway in HSC. Caffeine has a preventive effect on ALF. The mechanism may be interpreted that caffeine inhibits the cAMP/PKA/CREB signal pathway through adenosine A2A receptors in HSC. PMID:25701503

  8. On-treatment mortality predictors in chronic hepatitis B patients experiencing severe acute exacerbation: a prospective observational study

    PubMed Central

    2013-01-01

    Background Severe acute exacerbation in chronic hepatitis B could lead to mortality in some patients unless timely liver transplantation is performed. The baseline bilirubin level has been reported to be an important prognostic factor for mortality. Here we conducted a prospective observational study to examine the clinical performance of this predictor. Method Twenty-one consecutive chronic hepatitis B patients experiencing severe acute exacerbation were treated with either telbivudine or entecavir. The clinical characteristics at baseline and week-2 were documented and correlated with mortality. Results Of the 21 patients included, 9 had baseline bilirubin >10 mg/dL. Four of these 9 patients (44.4%) eventually died, whereas all other patients survived. During the initial 2-week period, the change of bilirubin was ?1.2 mg/dl in the survivors, but was +8.05 mg/dl in the mortalities (P = 0.009). When this on-treatment factor was combined, 5 of the 21 patients had baseline bilirubin > 10 mg/dL plus an increase of bilirubin level at week-2. Of these 5 patients, 4 (80%) died. Thus, by combining the baseline and on-treatment bilirubin levels, a positive predictive value of 80% and a negative predictive value of 100% could be achieved. Other significant on-treatment mortality predictors (at week-2) included higher international normalized ratio of prothrombin time (2.75 vs. 1.3, P = 0.004), higher model for end-stage liver disease score (30 vs. 17, P = 0.006), lower alpha-fetoprotein level (36.3 vs. 459.6 ng/mL, P = 0.039), and more rapid deterioration of the estimated glomerular filtration rate (eGFR) (P = 0.008). Interestingly, during the course, deterioration of eGFR was statistically significant in entecavir-treated (P = 0.028), but not in telbivudine-treated patients. Additionally, the patients treated with telbivudine had significant increase in serum alpha-fetoprotein (27.9 to 191.9 ng/ml, P = 0.046) in the first 2 weeks, whereas the corresponding feature was not found in those treated with entecavir (P = 0.139). Conclusions In this prospective observational study, we discovered that the baseline and on-treatment bilirubin levels should be combined to achieve a better predictive value. Telbivudine might have a renoprotective effect in addition to its efficacy in viral suppression in patients with severe acute exacerbation. PMID:24004574

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

    PubMed Central

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

    2015-01-01

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

  10. Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

    PubMed Central

    Gui, Bo; Hua, Fuzhou; Chen, Jie; Xu, Zeping; Sun, Hongbin; Qian, Yanning

    2014-01-01

    Oleanolic acid (OA) has been used to treat liver disorders, but whether it can attenuate hepatic ischemia-reperfusion- (IR-) associated liver dysfunction remains unexplored. In the present study, 160 male Sprague-Dawley rats were equally divided into five groups: group SH received neither hepatic IR nor drugs; group IR received hepatic IR without drugs; group CM and group OA received 0.5% sodium carboxymethylcellulose and 100?mg/kg OA, intragastrically, once a day for seven days before the hepatic IR, respectively; on the basis of treatment in group OA, group OA+wortmannin further received 15??g/kg of PI3K inhibitor wortmannin, intraperitoneally, 30?min before the hepatic IR. Then each group was equally divided into four subgroups according to four time points (preoperation, 0?h, 3?h, and 6?h after reperfusion). Serum ALT activity, IL-1? concentration, and hepatic phosphorylation of PI3K, Akt, and GSK-3? protein expression were serially studied. We found that OA pretreatment improved histological status and decreased serum ALT and IL-1? levels. It also increased p-PI3K, p-Akt, and p-GSK-3? protein expression at all the four time points. Prophylactic wortmannin partially reversed OA's protective effects. The data indicate that OA pretreatment protects liver from IR injury during the acute phase partially through PI3K/Akt-mediated inactivation of GSK-3?. PMID:24829521

  11. Testing strategy to identify cases of acute hepatitis C virus (HCV) infection and to project HCV incidence rates.

    PubMed

    Page-Shafer, Kimberly; Pappalardo, Brandee L; Tobler, Leslie H; Phelps, Bruce H; Edlin, Brian R; Moss, Andrew R; Wright, Teresa L; Wright, David J; O'Brien, Thomas R; Caglioti, Sally; Busch, Michael P

    2008-02-01

    Surveillance for hepatitis C virus (HCV) is limited by the challenge of differentiating between acute and chronic infections. In this study, we evaluate a cross-sectional testing strategy that identifies individuals with acute HCV infection and we estimate HCV incidence. Anti-HCV-negative persons from four populations with various risks, i.e., blood donors, Veterans Administration (VA) patients, young injection drug users (IDU), and older IDU, were screened for HCV RNA by minipool or individual sample nucleic acid testing (NAT). The number of detected viremic seronegative infections was combined with the duration of the preseroconversion NAT-positive window period (derived from analysis of frequent serial samples from plasma donors followed from NAT detection to seroconversion) to estimate annual HCV incidence rates. Projected incidence rates were compared to observed incidence rates. Projected HCV incidence rates per 100 person-years were 0.0042 (95% confidence interval [95% CI], 0.0025 to 0.007) for blood donors, 0.86 (95% CI, 0.02 to 0.71) for VA patients, 39.8 (95% CI, 25.9 to 53.7) for young IDU, and 53.7 (95% CI, 23.4 to 108.8) for older IDU. Projected rates were most similar to observed incidence rates for young IDU (33.4; 95% CI, 28.0 to 39.9). This study demonstrates the value of applying a cross-sectional screening strategy to detect acute HCV infections and to estimate HCV incidence. PMID:18032621

  12. Acute Alcohol Intake Induces SOCS1 and SOCS3 and Inhibits Cytokine-Induced STAT1 and STAT3 Signaling in Human Monocytes

    PubMed Central

    Norkina, Oxana; Dolganiuc, Angela; Catalano, Donna; Kodys, Karen; Mandrekar, Pranoti; Syed, Amber; Efros, Marian; Szabo, Gyongyi

    2014-01-01

    Background Acute alcohol consumption is associated with induction of immuno-inhibitory cytokines and down-regulation of pro-inflammatory responses to various pathogens. We previously reported that alcohol activates janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling leading to IL-10 induction. The JAK-STAT pathway also activates its own negative regulators, suppressors of cytokine signaling (SOCS) 1 and SOCS3. SOCS proteins are inducible inhibitors that negatively regulate STAT3/STAT1 signaling pathways induced by cytokines, IL-6 or IFNs. Here we aimed to explore the effect of acute alcohol on induction of SOCS1/SOCS3 and regulation of STAT3/STAT1 pathways induced by IL-6 or IFNs in human monocytes. Methods Blood samples from normal volunteers were collected before and 24 hours after consumption of 2 ml vodka/kg body weight. For in vitro experiments human monocytes were pretreated with ethanol (EtOH) followed by stimulation with cytokines; proteins were analyzed by Western blot, nuclear protein binding to DNA by EMSA, and RNA by real time PCR. Results: Acute in vivo or in vitro alcohol treatment increased both SOCS1 and SOCS3 RNA expression in monocytes. Alcohol treatment resulted in increased STAT3 and STAT1 DNA binding capacity. Activation of both STAT1 and STAT3 has been shown to induce SOCS1/3. We hypothesized that induction of SOCS proteins by alcohol in turn may lead to modulation of cytokine signaling through STAT1 and STAT3. Indeed, we observed significant down-regulation of IL-6-, IFN?- and IFN?-induced STAT1 DNA binding as well as inhibition of IL-6- and IFN?-induced STAT3 when alcohol was added to monocytes 3 hours prior to the cytokine stimulation. Consistent with inhibition of IL-6-induced STAT3 DNA binding in alcohol-pretreated cells, the levels of IL-6-dependent genes, MCP-1 and ICAM-1, was reduced after IL-6 stimulation. Similar to EtOH alone, combined EtOH+IL-6 simulation resulted in increased expression of both SOCS3 and SOCS1 genes. Conclusion While acute alcohol treatment alone activates STAT1/3 signaling pathways and induces SOCS3 and SOCS1 levels in monocytes, alcohol also leads to down-regulation of IL-6-, IFN?-, and IFN?-induced signaling via STAT1/STAT3 pathways, likely through excessive SOCS activation. PMID:18616672

  13. A case of cholestatic hepatitis associated with histologic features of acute cholangitis

    PubMed Central

    Takeuchi, Hajime; Kaneko, Toru; Otsuka, Toshikazu; Tahara, Kumiko; Motoori, Tadashi; Ohbu, Makoto; Oda, Masaya; Yokomori, Hiroaki

    2011-01-01

    This report describes a case showing histologic features of acute cholangitis with an over-the-counter drug. A 48-year-old woman was diagnosed with general malaise and progressive jaundice. A thorough review of her medical history revealed that the patient had taken an over-the-counter drug, Pabron Gold®, which she had used previously, that may have caused liver injury. Laboratory investigations revealed jaundice and liver dysfunction. Endoscopic retrograde cholangiography detected no extrahepatic biliary duct dilatation or stones. Liver biopsy indicated acute cholangitis involving neutrophils and eosinophils. Electron microscopy revealed fragmented nuclei, indicating that the degenerative bile duct-related epithelial cells were in an apoptotic process. PMID:22162934

  14. Acute and residual effects of alcohol and marijuana, alone and in combination, on mood and performance

    Microsoft Academic Search

    L. D. Chait; J. L. Perry

    1994-01-01

    The duration of behavioral impairment after marijuana smoking remains a matter of some debate. Alcohol and marijuana are frequently used together, but there has been little study of the effects of this drug combination on mood and behavior the day after use. The present study was designed to address these issues. Fourteen male and female subjects were each studied under

  15. Heart Rate Variability and Sympathetic Skin Response in Male Patients Suffering From Acute Alcohol Withdrawal Syndrome

    Microsoft Academic Search

    Karl-Jurgen Bar; Michael Karl Boettger; Rene Neubauer; Marei Groteluschen; Thomas Jochum; Vico Baier; Heinrich Sauer; Andreas Voss

    2006-01-01

    Background: Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. Methods: We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients

  16. Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

    PubMed Central

    Chang, Hua-Ming; Liao, Yi-Wen; Chiang, Chih-Hung; Chen, Yi-Jen; Lai, Ying-Hsiu; Chang, Yuh-Lih; Chen, Hen-Li; Jeng, Shaw-Yeu; Hsieh, Jung-Hung; Peng, Chi-Hsien; Li, Hsin-Yang; Chien, Yueh; Chen, Szu-Yu; Chen, Liang-Kung; Huo, Teh-Ia

    2012-01-01

    The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases. PMID:22489170

  17. Circulating microRNAs: promising candidates serving as novel biomarkers of acute hepatitis

    PubMed Central

    Elfimova, Natalia; Schlattjan, Martin; Sowa, Jan-Peter; Dienes, Hans Peter; Canbay, Ali; Odenthal, Margarete

    2012-01-01

    Acute liver failure as life threatening condition comprises a difficult diagnostic situation to evaluate potential outcomes and therapeutic options. Thus, prognostic indicators are urgently needed for evaluation of progression of liver injury, clinical outcome, prognosis, and for therapeutic response. Recently, circulating microRNA, in particular miR-122, was described as a potential biomarker of acute liver injury after intoxication of mice. Circulating microRNA (miRNA) molecules are very stable and RNase-resistant due to protein aggregation and vesicle enclosure. Since miRNA species are known to be associated with chronic liver damage or with liver cancer, circulating miRNA patterns are suggested to serve also as reporters for progression of acute liver failure. miRNA profiling analyses using PCR arrays or next generation sequencing, may achieve identification of miRNA species that are linked to the rapid progression of acute liver injury, to the outcome of liver failure, or to the therapeutic response. Therefore, circulating miRNAs are promising, non-invasive biomarkers of future diagnostic approaches. However, normalisation of circulating miRNA levels is essential and further standardisation of miRNA quantification assays is needed. PMID:23267332

  18. Protective effect of Zhuyeqing liquor, a Chinese traditional health liquor, on acute alcohol-induced liver injury in mice

    PubMed Central

    2013-01-01

    The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL) against acute alcohol-induced liver injury in mice. Animals were administered orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for fourteen consecutive days except mice in normal group. The protective effect was evaluated by biochemical parameters including serum aspartate transaminase (AST), alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result were confirmed histopathologically and the expression of TNF-? in mice liver was determined by immunohistochemistry analysis. HPLC-PDA was used for phytochemical analysis of ZYQL, and the plant source of each compound was claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes in a dose depended manner. HPLC analysis indicated that ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might be the active chemicals. This study demonstrated the hepatoprotective activity of ZYQL, thus scientifically supported the function of its health care. PMID:24090365

  19. Acute hepatic sequestration associated with pneumococcal infection in a 5-year-old Boy with sickle beta degrees -thalassemia: a case report and review of the literature.

    PubMed

    Ahmed, Nabil; Chizhevsky, Vladislav

    2007-10-01

    A 5-year-old black male with sickle beta degrees -thalassemia presented with fever and a vaso-occlusive crisis. Within hours, he developed progressive hepatomegaly with an acute drop in the hemoglobin level that was refractory to repeated red blood cell transfusion. His condition deteriorated and eventually he succumbed to cardiorespiratory failure related to sepsis. Blood cultures grew Streptococcus pneumoniae. To the best of our knowledge, this is the first reported case of hepatic sequestration in a young child and the first reported in a patient with sickle beta degrees -thalassemia. We describe here the clinicohematologic and pathologic features of this case consistent with acute hepatic sequestration and present a review of the relevant literature. PMID:17921856

  20. Deficiencies in the Acute-Phase Cell-Mediated Immune Response to Viral Antigens Are Associated with Development of Chronic Woodchuck Hepatitis Virus Infection following Neonatal Inoculation

    PubMed Central

    Menne, Stephan; Roneker, Carol A.; Roggendorf, Michael; Gerin, John L.; Cote, Paul J.; Tennant, Bud C.

    2002-01-01

    In vitro proliferation of peripheral blood mononuclear cells was used to measure virus-specific cell-mediated immunity (vCMI) following neonatal woodchuck hepatitis virus (WHV) infection. Fifteen neonates were inoculated with the W8 strain of WHV. In 11, infection was resolved, and 4 became chronic carriers. Nineteen neonates were inoculated with the W7 strain and all became chronic carriers. Seven age-matched uninfected woodchucks served as controls. Virologic and vCMI profiles among the W8 and W7 infections were compared and related to the outcome of infection. Resolving woodchucks had robust, acute-phase vCMI to WHV antigens (core, surface, and x) and to several nonoverlapping core peptides. The acute-phase vCMI was associated temporally with the clearance of viral DNA and of surface antigen from serum at 14 to 22 weeks postinfection. In contrast, in approximately half of the W8 and W7 infections that progressed to chronicity, no significant acute-phase vCMI was detected. In the remaining carriers, acute-phase vCMI was observed, but it was less frequent and incomplete compared to that of resolved woodchucks. Serum viral load developed less rapidly in those carriers that had evidence of acute-phase vCMI, but it was still increased compared to that of resolving woodchucks. Thus, vigorous and multispecific acute-phase vCMI was associated with resolution of neonatal WHV infection. Absent or incomplete acute-phase vCMI was associated with the progression to chronic infection. By analogy, these results suggest that the onset of chronic hepatitis B virus (HBV) infection in humans may be associated with deficiencies in the primary T-cell response to acute HBV infection. PMID:11799172

  1. Alcohol and Hepatitis C

    MedlinePLUS

    ... Performance VA Plans, Budget, & Performance VA Center for Innovation (VACI) Performance and Accountability Report Budget Submission Recovery Act Resources Explore your VA Benefits Business Congressional Affairs Jobs Benefits Booklet Data & Statistics National ...

  2. Effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration, ROS production and lipid peroxidation in broiler chickens

    Microsoft Academic Search

    Lin Yang; Gao-Yi Tan; Yu-Qiang Fu; Jin-Hai Feng; Min-Hong Zhang

    2010-01-01

    In order to investigate the effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration, production of reactive oxygen species (ROS) and lipid peroxidation in broiler chickens, 128 six-week-old broiler chickens were kept in a controlled-environment chamber. The broiler chickens were initially kept at 25°C (relative humidity, RH, 70±5%) for 6d and subsequently exposed to

  3. Putative cis-Acting Stem-Loops in the 5' Untranslated Region of the Severe Acute Respiratory Syndrome Coronavirus Can Substitute for Their Mouse Hepatitis Virus Counterparts

    Microsoft Academic Search

    Hyojeung Kang; Min Feng; Megan E. Schroeder; David P. Giedroc; Julian L. Leibowitz

    2006-01-01

    Consensus covariation-based secondary structural models for the 5! 140 nucleotides of the 5! untranslated regions (5! UTRs) from mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SCoV) were developed and predicted three major helical stem-loop structures, designated stem-loop 1 (SL1), SL2, and SL4. The SCoV 5! UTR was predicted to contain a fourth stem-loop, named SL3, in which

  4. Comparison of portal vein velocity and the hepatic venous pressure gradient in assessing the acute portal hemodynamic response to propranolol in patients with cirrhosis

    Microsoft Academic Search

    Michael Schepke; Peter Raab; Alexander Hoppe; Peter Schiedermaier; Karl-August Brensing; Tilman Sauerbruch

    2000-01-01

    OBJECTIVE:The aim of this prospective study was to compare noninvasive Doppler sonography and invasive measurement of the hepatic venous pressure gradient (HVPG) to determine the acute portal hemodynamic response to propranolol in patients with liver cirrhosis.METHODS:In a blinded study design, portal vein velocity (PVV) and HVPG were simultaneously assessed in 11 cirrhotic patients for 4 h after oral ingestion of

  5. Effects of methanol extract of Cirsium japonicum var. ussuriense and its principle, hispidulin-7-O-neohesperidoside on hepatic alcohol-metabolizing enzymes and lipid peroxidation in ethanol-treated rats.

    PubMed

    Park, Jong Cheol; Hur, Jong Moon; Park, Ju Gwon; Kim, Sang Cheol; Park, Jeong Ro; Choi, Seong Hee; Choi, Jong Won

    2004-01-01

    Effects of the methanol extract of Cirsium japonicum var. ussuriense and hispidulin 7-O-neohesperidoside isolated from the plant on hepatic alcohol-metabolizing enzymes and lipid peroxidation were studied in rats treated with ethanol. Rats treated with 10% alcohol solution for 6 weeks were orally administered with 250 or 500 mg of methanol extract or 10 or 20 mg of hispidulin 7-O-neohesperidoside per kg body weight daily during the last week of ethanol treatment. The administration of the methanol extract of herbal plant and hispidulin 7-O-neohesperidoside in ethanol-treated rats significantly enhanced the activities of hepatic alcohol dehydrogenase, microsomal ethanol-oxidizing system and aldehyde dehydrogenase in a dose-dependent manner. The extract and the compound decreased hepatic lipid peroxidation along with an increase in hepatic content of reduced glutathione. The methanol extract and hispidulin 7-O-neohesperidoside of C. japonicum var. ussuriense also increased the activity of glutathione reductase, but had no effect on gamma-glutamylcysteine synthase. The results suggest that C. japonicum var. ussuriense may alleviate alcoholic toxicity by enhancing ethanol oxidation as well as inhibiting lipid peroxidation, and hispidulin 7-O-neohesperidoside is one of the active substances responsible for the protective effects of this plant. PMID:14750195

  6. Acute Alcohol Intoxication and Suicide Among U.S. Ethnic/Racial Groups: Findings from the National Violent Death Reporting System

    PubMed Central

    Caetano, Raul; Kaplan, Mark S.; Huguet, Nathalie; McFarland, Bentson H.; Conner, Kenneth; Giesbrecht, Norman; Nolte, Kurt B.

    2012-01-01

    Background To assess the prevalence and sociodemographic correlates of suicide involving acute alcohol intoxication among U.S. ethnic minorities. Methods Data were derived from the restricted 2003–2009 National Violent Death Reporting System (NVDRS). The study focused on the sociodemographic and toxicological information of 59,384 male and female suicide decedents for 16 states of the U.S. Acute alcohol intoxication was defined as having a blood alcohol content (BAC) ? 0.08 g/dl. Overall, 76% of decedents were tested for the presence of alcohol. Results The proportion of suicide decedents with a positive BAC ranged from 47% among American Indians/Alaska Natives (AIs/ANs) to 23% among Asians/Pacific Islanders (PIs). Average BAC was highest among AIs/ANs. Among those who were tested for BAC, the proportion of decedents legally intoxicated prior to suicide was: Blacks, 15%; AIs/ANs, 36%; Asians/PIs, 13%; Hispanics, 28%. Bivariate associations showed that most suicide decedents who were legally intoxicated were male, younger than 30 years of age, with a high school education, not married, non-veterans, lived in metropolitan areas, and used a firearm to complete suicide. However, with the exception of Whites, most of these associations became not statistically significant in multivariate analysis. Conclusions Alcohol use and legal intoxication prior to completing suicide are common among U.S. ethnic groups, especially among males and those who are younger than 30 years of age. The AI/AN group had the highest mean BAC, the highest rate of legal intoxication and decedents who were particularly young. Suicide prevention strategies should address alcohol use as a risk factor. Alcohol problems prevention strategies should focus on suicide as a consequence of alcohol use, especially among AI/AN youth and young adults. PMID:23384174

  7. Acute allograft rejection following interferon therapy for hepatitis C in recipients who have returned to dialysis after kidney transplant failure: case study.

    PubMed

    Fabrizi, Fabrizio; D'Ambrosio, Roberta; Pallotti, Francesco; Berardinelli, Luisa; Messa, Piergiorgio; Martin, Paul; Aghemo, Alessio

    2014-11-01

    Interferon-based therapy remains the gold standard for hepatitis C in patients with chronic kidney disease; however, due to the high rate of IFN-induced rejection after transplant, treatment of HCV-infected kidney transplant recipients is recommended only in particular circumstances. We report the case of a 45-year-old Caucasian female with chronic hepatitis C (genotype 1b) who returned to hemodialysis following the complete functional loss of her kidney transplant. She started combination antiviral therapy with peg-IFN-?2a (135 mcg sc weekly) plus ribavirin (200 mg daily) nine months after the re-initiation of hemodialysis. Antiviral therapy was neither effective nor safe; ribavirin was stopped at week 38 due to hemolytic anemia; on-treatment HCV breakthrough was observed at week 48; and acute rejection occurred after four months of IFN-based therapy. Diagnosis of acute allograft rejection was suspected on the grounds of clinical, radiographic, and laboratory data. Allograft nephrectomy was then performed and histology showed acute-on-chronic rejection. This is an uncommon case of IFN-associated kidney rejection in an allograft recipient who had functional loss of her graft and had returned to hemodialysis. In view of the risk of rejection of renal allograft, and the limited efficacy of IFN-based treatment of hepatitis C, physicians should be aware of effective treatment with oral anti-viral agents and avoid the use of IFN in patients on maintenance dialysis with failed renal allograft. PMID:25362901

  8. Regarding the fitness to ride a bicycle under the acute influence of alcohol.

    PubMed

    Hartung, Benno; Mindiashvili, Nona; Maatz, Rüdiger; Schwender, Holger; Roth, Eckhard H; Ritz-Timme, Stefanie; Moody, Justin; Malczyk, Axel; Daldrup, Thomas

    2015-05-01

    To determine the threshold for the absolute inability to ride a bicycle, practical cycling tests and medical examinations at different blood alcohol concentrations were performed. Special attention was given to additional medical examinations, reaction tests and alcohol consumption under real-life conditions. Seventy-eight test subjects were included in the trials (37 females, 41 males). Five test subjects participated twice; thus, there were a total of 83 evaluable trials. Alcohol-related deficits were already identifiable at very low BACs. A significant increase in gross motoric disturbances compared to the soberness state did not regularly occur until a BAC of at least 0.8 g/kg was reached. At the BAC of 1.4 g/kg and above, no test subjects were able to achieve or surpass their sober driving results. Isolated highly alcoholised test subjects rode the bike in a manner that was not conspicuously different than the other sober test persons. Contrary to the assumptions of current German legal practise, it cannot be stated that all people are 'absolutely impaired' to the point of being incapable of riding bicycle at BACs of at least 1.6 g/kg. PMID:25428289

  9. Protective effect of mesenchymal stem cell-conditioned medium on hepatic cell apoptosis after acute liver injury.

    PubMed

    Xagorari, Angeliki; Siotou, Eleni; Yiangou, Minas; Tsolaki, Eleftheria; Bougiouklis, Dimitris; Sakkas, Leonidas; Fassas, Athanassios; Anagnostopoulos, Achilles

    2013-01-01

    The aim of this study was to investigate the role of Mesenchymal Stem Cell (MSC) conditioned medium (CM(MSC)) on apoptosis of cultured mouse primary hepatocytes after in vivo carbon tetrachloride (CCl4)-induced acute liver injury. The acute liver injury was induced by injecting CCl4 intraperitoneally in C57/BL6 mice. Hepatocytes were isolated by liver perfusion, cultured in a defined medium to maintain their differentiation and characterized by reverse transcriptase polymerase chain reaction (RT-PCR) using the hepatic cell specific genes albumin, hepatocyte nuclear factor 4 (HNF4) and cytokeratin 18 (CK18). CM(MSC) was generated from cultured bone marrow-derived MSCs (BM-MSCs). BM-MSCs were positive for CD73, CD90, CD44 by flow cytometry and able to differentiate into chondrocytes, adipocytes and osteocytes. Apoptosis was evaluated by both annexin V. CM(MSC) were examined by flow cytometry to detect MSC-derived annexin V- and CD54/CD44-positive microparticles (MPs). In the CCl4-CM(MSC) treated hepatocytes, interleukin-6 (IL-6) was increased on the first day of culture compared to control and CCl4 and was followed by upregulation of fibroblast-like-protein (FGL1) expression after 48 hrs. This was associated with a significant decrease of annexin V positive CCl4-CM(MSC) treated hepatocytes at day 3 post plating. Recombinant IL-6 was induced FGL1 expression in hepatocytes derived from CCl4-treated mice suggesting that CM(MSC), which is enriched also in microparticles, attenuates CCl4-induced early apoptosis in hepatocytes through activation of FGL1. PMID:23638214

  10. V?14iNKT cell Deficiency Prevents Acetaminophen-Induced Acute Liver Failure by Enhancing Hepatic Glutathione and Altering APAP Metabolism

    PubMed Central

    Downs, Isaac; Aw, Tak Yee; Liu, Jianfeng; Adegboyega, Patrick; Ajuebor, Maureen N.

    2012-01-01

    Acetaminophen (APAP) overdose is widely regarded as a major cause of acute liver failure in the United States. Intentional or accidental overdose of APAP in man or rodent elicits direct hepatocellular injury that is accompanied by hepatic depletion of the antioxidant, glutathione (GSH). In recent years, the innate immune response has also been shown to promote the development of APAP hepatotoxicity via indirect liver damage. In the present study, we demonstrate that J?18?/? mice, which are selectively deficient in the innate immune T cell, V?14iNKT cells, were resistant to APAP hepatotoxicity relative to WT mice as reflected by biochemical and histological liver injury markers. In parallel, improvement in the biochemical and histological parameters of liver injury in J?18?/? mice was associated with a significant increase in hepatic levels of GSH, which detoxified APAP metabolites to attenuate hepatic oxidative stress, liver injury and necrosis. Notably, the protective effect of hepatic GSH during V?14iNKT cells deficiency was demonstrated by its depletion in J?18?/? mice using DL-buthionine-[S,R]-sulfoximine which exacerbated hepatic oxidative and nitrosative stress as well as liver necrosis and caused mice mortality. Extraordinarily, APAP metabolism in J?18?/? mice was altered in favor of hepatic GSH conjugates and decreased glucuronide conjugates. In summary, we reveal a novel finding establishing a unique association between hepatic innate immunity and GSH levels in altering APAP metabolism to suppress liver injury and necrosis during V?14iNKT cells deficiency in J?18?/? mice. PMID:23079619

  11. Spatio-temporal processing of words and nonwords: hemispheric laterality and acute alcohol intoxication.

    PubMed

    Marinkovic, Ksenija; Rosen, Burke Q; Cox, Brendan; Hagler, Donald J

    2014-04-16

    This study examined neurofunctional correlates of reading by modulating semantic, lexical, and orthographic attributes of letter strings. It compared the spatio-temporal activity patterns elicited by real words (RW), pseudowords, orthographically regular, pronounceable nonwords (PN) that carry no meaning, and orthographically illegal, nonpronounceable nonwords (NN). A double-duty lexical decision paradigm instructed participants to detect RW while ignoring nonwords and to additionally respond to words that refer to animals (AW). Healthy social drinkers (N=22) participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. Whole-head MEG signals were analyzed with an anatomically-constrained MEG method. Simultaneously acquired ERPs confirm previous evidence. Spatio-temporal MEG estimates to RW and PN are consistent with the highly replicable left-lateralized ventral visual processing stream. However, the PN elicit weaker activity than other stimuli starting at ~230 ms and extending to the M400 (magnetic equivalent of N400) in the left lateral temporal area, indicating their reduced access to lexicosemantic stores. In contrast, the NN uniquely engage the right hemisphere during the M400. Increased demands on lexicosemantic access imposed by AW result in greater activity in the left temporal cortex starting at ~230 ms and persisting through the M400 and response preparation stages. Alcohol intoxication strongly attenuates early visual responses occipito-temporally overall. Subsequently, alcohol selectively affects the left prefrontal cortex as a function of orthographic and semantic dimensions, suggesting that it modulates the dynamics of the lexicosemantic processing in a top-down manner, by increasing difficulty of semantic retrieval. PMID:24565928

  12. Specificity of an Anti-Capsid Antibody Associated with Hepatitis B Virus-Related Acute Liver Failure

    PubMed Central

    Wu, Weimin; Chen, Zhaochun; Cheng, Naiqian; Watts, Norman R.; Stahl, Stephen J.; Farci, Patrizia; Purcell, Robert H.; Wingfield, Paul T.; Steven, Alasdair C.

    2012-01-01

    Previously, the livers of patients suffering from acute liver failure (ALF), a potentially fatal syndrome arising from infection by Hepatitis B Virus (HBV), were found to contain massive amounts of an antibody specific for the core antigen (HBcAg) capsid. We have used cryo-electron microscopy and molecular modeling to define its epitope. HBV capsids are icosahedral shells with 25Å-long dimeric spikes, each a 4-helix bundle, protruding from the contiguous “floor”. Of the anti-HBcAg antibodies previously characterized, most bind around the spike tip while one binds to the floor. The ALF-associated antibody binds tangentially to a novel site on the side of the spike. This epitope is conformational. The Fab binds with high affinity to its principal determinants but has lower affinities for quasi-equivalent variants. The highest occupancy site is on one side of a spike, with no detectable binding to the corresponding site on the other side. Binding of one Fab per dimer was also observed by analytical ultracentrifugation. The Fab did not bind to the e-antigen dimer, a non-assembling variant of capsid protein. These findings support the propositions that antibodies with particular specificities may correlate with different clinical expressions of HBV infection and that antibodies directed to particular HBcAg epitopes may be involved in ALF pathogenesis. PMID:23079477

  13. Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein

    PubMed Central

    Anderson, Sheila A.; Wang, Jiaohong; Yang, Fan; DeMaster, Kristina; Ahmed, Riffat; Nizzi, Christopher P.; Eisenstein, Richard S.; Tsukamoto, Hidekazu; Enns, Caroline A.

    2011-01-01

    Recent studies demonstrate a pivotal role for bone morphogenic protein-6 (BMP6) and matriptase-2, a protein encoded by the TMPRSS6 gene, in the induction and suppression of hepatic hepcidin expression, respectively. We examined their expression profiles in the liver and showed a predominant localization of BMP6 mRNA in nonparenchymal cells and exclusive expression of TMPRSS6 mRNA in hepatocytes. In rats fed an iron-deficient (ID) diet for 24 hours, the rapid decrease of transferrin saturation from 71% to 24% (control vs ID diet) was associated with a 100-fold decrease in hepcidin mRNA compared with the corresponding controls. These results indicated a close correlation of low transferrin saturation with decreased hepcidin mRNA. The lower phosphorylated Smad1/5/8 detected in the ID rat livers suggests that the suppressed hepcidin expression results from the inhibition of BMP signaling. Quantitative real-time reverse transcription polymerase chain reaction analysis revealed no significant change in either BMP6 or TMPRSS6 mRNA in the liver. However, an increase in matriptase-2 protein in the liver from ID rats was detected, suggesting that suppression of hepcidin expression in response to acute iron deprivation is mediated by an increase in matriptase-2 protein levels. PMID:21115976

  14. The peritoneal macrophage inflammatory profile in cirrhosis depends on the alcoholic or hepatitis C viral etiology and is related to ERK phosphorylation

    PubMed Central

    2012-01-01

    Background The development of ascites in cirrhotic patients generally heralds a deterioration in their clinical status. A differential gene expression profile between alcohol- and hepatitis C virus (HCV)-related cirrhosis has been described from liver biopsies, especially those associated with innate immune responses. The aim of this work was to identify functional differences in the inflammatory profile of monocyte-derived macrophages from ascites in cirrhotic patients of different etiologies in an attempt to extrapolate studies from liver biopsies to immune cells in ascites. To this end 45 patients with cirrhosis and non-infected ascites, distributed according to disease etiology, HCV (n?=?15) or alcohol (n?=?30) were studied. Cytokines and the cell content in ascites were assessed by ELISA and flow cytometry, respectively. Cytokines and ERK phosphorylation in peritoneal monocyte-derived macrophages isolated and stimulated in vitro were also determined. Results A different pattern of leukocyte migration to the peritoneal cavity and differences in the primed status of macrophages in cirrhosis were observed depending on the viral or alcoholic etiology. Whereas no differences in peripheral blood cell subpopulations could be observed, T lymphocyte, monocyte and polymorphonuclear cell populations in ascites were more abundant in the HCV than the alcohol etiology. HCV-related cirrhosis etiology was associated with a decreased inflammatory profile in ascites compared with the alcoholic etiology. Higher levels of IL-10 and lower levels of IL-6 and IL-12 were observed in ascitic fluid from the HCV group. Isolated peritoneal monocyte-derived macrophages maintained their primed status in vitro throughout the 24 h culture period. The level of ERK1/2 phosphorylation was higher in ALC peritoneal macrophages at baseline than in HCV patients, although the addition of LPS induced a greater increase in ERK1/2 phosphorylation in HCV than in ALC patients. Conclusions The macrophage inflammatory status is higher in ascites of alcohol-related cirrhotic patients than in HCV-related patients, which could be related with differences in bacterial translocation episodes or regulatory T cell populations. These findings should contribute to identifying potential prognostic and/or therapeutic targets for chronic liver diseases of different etiology. PMID:22866973

  15. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

    PubMed Central

    Kanter, Mehmet; Demir, Halit; Karakaya, Cengiz; Ozbek, Hanefi

    2005-01-01

    AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an exper-imental model. METHODS: Male Wistar albino rats were assigned into 4 groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis. RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue. CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity. PMID:16425361

  16. In vivo ethanol elimination in man, monkey and rat: A lack of relationship between the ethanol metabolism and the hepatic activities of alcohol and aldehyde dehydrogenases

    SciTech Connect

    Zorzano, A. (Universidad de Barcelona (Spain)); Herrera, E. (Universidad de Madrid (Spain))

    1990-01-01

    The in vivo ethanol elimination in human subjects, monkeys and rats was investigated after an oral ethanol dosage. After 0.4 g. ethanol/kg of body weight, ethanol elimination was much slower in human subjects than in monkeys. In order to detect a rise in monkey plasma ethanol concentrations as early as observed in human subjects, ethanol had to be administered at a dose of 3 g/kg body weight. Ethanol metabolism in rats was also much faster than in human subjects. However, human liver showed higher alcohol dehydrogenase activity and higher low Km aldehyde dehydrogenase activity than rat liver. Thus, our data suggest a lack of relationship between hepatic ethanol-metabolizing activities and the in vivo ethanol elimination rate.

  17. Subinfectious Hepatitis C Virus Exposures Suppress T cell Responses Against Subsequent Acute Infection

    PubMed Central

    Park, Su–Hyung; Veerapu, Naga Suresh; Shin, Eui–Cheol; Biancotto, Angélique; McCoy, J. Philip; Capone, Stefania; Folgori, Antonella; Rehermann, Barbara

    2013-01-01

    Summary Hepatitis C virus (HCV) is endemic in many countries due to its high propensity to establish persistence1. The presence of HCV–specific T cells in repeatedly HCV–exposed subjects who test for HCV RNA and antibodies and do not have any history of HCV infection has been interpreted as T cell–mediated protection2-5. Here, we show in nonhuman primates that repeated exposure to human plasma with trace amounts of HCV induced HCV–specific T cells without seroconversion and systemic viremia, but did not protect upon subsequent HCV challenge. Rather, HCV–specific recall and de novo T cell responses as well as intrahepatic T cell recruitment and IFN-? production were suppressed upon HCV challenge, concomitant to quantitative and qualitative changes in regulatory T (Treg) cells that began after subinfectious HCV exposure and increased after HCV challenge. In vitro Treg cell depletion restored HCV–specific T cell responses. Thus, T cells primed by trace amounts of HCV do not generate effective recall responses upon subsequent HCV infection. Subinfectious HCV exposure predisposes to Treg cell expansion, which suppresses effector T cells during subsequent infection. Strategies to reverse this exposure–induced suppression should be examined to aid the development of T cell–based vaccines against HCV and other endemic pathogens. PMID:24270546

  18. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Yu, Haoyong; Jia, Weiping; Guo, ZengKui

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. Results the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment. PMID:25411646

  19. Indirect Effects of Acute Alcohol Intoxication on Sexual Risk-taking: The Roles of Subjective and Physiological Sexual Arousal

    Microsoft Academic Search

    William H. George; Kelly Cue Davis; Jeanette Norris; Julia R. Heiman; Susan A. Stoner; Rebecca L. Schacht; Christian S. Hendershot; Kelly F. Kajumulo

    2009-01-01

    Three experiments supported the idea that alcohol fosters sexual risk-taking in men and women, in part, through its effects\\u000a on sexual arousal. In Experiment 1, increasing alcohol dosage (target blood alcohol levels of .00, .04, .08%) heightened men’s\\u000a and women’s risk-taking intentions. Alcohol’s effect was indirect via increased subjective sexual arousal; also, men exhibited\\u000a greater risk-taking than women. In Experiment

  20. Alcoholic Lung Injury: Metabolic, Biochemical and Immunological Aspects

    PubMed Central

    Kaphalia, Lata; Calhoun, William J.

    2013-01-01

    Chronic alcohol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). A significant amount of ingested alcohol reaches airway passages in the lungs and can be metabolized via oxidative and non-oxidative pathways. About 90% of the ingested alcohol is metabolized via hepatic alcohol dehydrogenase (ADH)-catalyzed oxidative pathway. Alcohol can also be metabolized by cytochrome P450 2E1 (CYP2E1), particularly during chronic alcohol abuse. Both the oxidative pathways, however, are associated with oxidative stress due to the formation of acetaldehyde and/or reactive oxygen species (ROS). Alcohol ingestion is also known to cause endoplasmic reticulum (ER) stress, which can be mediated by oxidative and/or non-oxidative metabolites of ethanol. An acute as well as chronic alcohol ingestions impair protective antioxidants, oxidize reduced glutathione (GSH, cellular antioxidant against ROS and oxidative stress), and suppress innate and adaptive immunity in the lungs. Oxidative stress and suppressed immunity in the lungs of chronic alcohol abusers collectively are considered to be major risk factors for infection and development of pneumonia, and such diseases as ARDS and COPD. Prior human and experimental studies attempted to identify common mechanisms by which alcohol abuse directly causes toxicity to alveolar epithelium and respiratory tract, particularly lungs. In this review, the metabolic basis of lung injury, oxidative and ER stress and immunosuppression in experimental models and alcoholic patients, as well as potential immunomodulatory therapeutic strategies for improving host defenses against alcohol-induced pulmonary infections are discussed. PMID:23892124

  1. MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke's Encephalopathy: A Review

    PubMed Central

    Manzo, Gaetana; De Gennaro, Angela; Cozzolino, Attilio; Serino, Antonietta; Fenza, Giacomo; Manto, Andrea

    2014-01-01

    Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. Apart from chronic alcoholism, the most common cause of WE, a lot of other conditions causing malnutrition and decreasing thiamine absorption such as gastrointestinal surgical procedures and hyperemesis gravidarum must be considered as predisposing factors. Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed, leading to persistent dysfunctions and, in some cases, to death. Nowadays, MR imaging of the brain, showing T2 and FLAIR hyperintensities in typical (thalami, mammillary bodies, tectal plate, and periaqueductal area) and atypical areas (cerebellum, cranial nerve nuclei, and cerebral cortex), is surely the most important and effective tool in the diagnostic assessment of WE. The aim of this paper is to propose a state of the art of the role of MR imaging in the early diagnosis of this complex disease. PMID:25050351

  2. Lycium barbarum polysaccharides therapeutically improve hepatic functions in non-alcoholic steatohepatitis rats and cellular steatosis model.

    PubMed

    Xiao, Jia; Xing, Feiyue; Huo, Jie; Fung, Man Lung; Liong, Emily C; Ching, Yick Pang; Xu, Aimin; Chang, Raymond Chuen Chung; So, Kwok Fai; Tipoe, George L

    2014-01-01

    This study aimed to investigate the possible therapeutic effects and active components of Lycium barbarum polysaccharides (LBP) on a high fat diet-induced NASH rat model. We induced NASH in a rat model by voluntary oral feeding with a high-fat diet ad libitum for 8 weeks. After 8 weeks, 1?mg/kg LBP was orally administered for another 4 weeks with a high-fat diet. When compared with NASH rats treated for 12 weeks, therapeutic LBP treatment for 4 weeks during 12 weeks of NASH induction showed ameliorative effects on: (1) increased body and wet liver weights; (2) insulin resistance and glucose metabolic dysfunction; (3) elevated level of serum aminotransferases; (4) fat accumulation in the liver and increased serum free fatty acid (FFA) level; (5) hepatic fibrosis; (6) hepatic oxidative stress; (7) hepatic inflammatory response; and (8) hepatic apoptosis. These improvements were partially through the modulation of transcription factor NF-?B, MAPK pathways and the autophagic process. In a palmitate acid-induced rat hepatocyte steatosis cell-based model, we also demonstrated that l-arabinose and ?-carotene partially accounted for the beneficial effects of LBP on the hepatocytes. In conclusion, LBP possesses a variety of hepato-protective properties which make it a potent supplementary therapeutic agent against NASH in future clinical trials. PMID:24998389

  3. Lycium barbarum polysaccharides therapeutically improve hepatic functions in non-alcoholic steatohepatitis rats and cellular steatosis model

    PubMed Central

    Xiao, Jia; Xing, Feiyue; Huo, Jie; Fung, Man Lung; Liong, Emily C.; Ching, Yick Pang; Xu, Aimin; Chang, Raymond Chuen Chung; So, Kwok Fai; Tipoe, George L.

    2014-01-01

    This study aimed to investigate the possible therapeutic effects and active components of Lycium barbarum polysaccharides (LBP) on a high fat diet-induced NASH rat model. We induced NASH in a rat model by voluntary oral feeding with a high-fat diet ad libitum for 8 weeks. After 8 weeks, 1?mg/kg LBP was orally administered for another 4 weeks with a high-fat diet. When compared with NASH rats treated for 12 weeks, therapeutic LBP treatment for 4 weeks during 12 weeks of NASH induction showed ameliorative effects on: (1) increased body and wet liver weights; (2) insulin resistance and glucose metabolic dysfunction; (3) elevated level of serum aminotransferases; (4) fat accumulation in the liver and increased serum free fatty acid (FFA) level; (5) hepatic fibrosis; (6) hepatic oxidative stress; (7) hepatic inflammatory response; and (8) hepatic apoptosis. These improvements were partially through the modulation of transcription factor NF-?B, MAPK pathways and the autophagic process. In a palmitate acid-induced rat hepatocyte steatosis cell–based model, we also demonstrated that l-arabinose and ?-carotene partially accounted for the beneficial effects of LBP on the hepatocytes. In conclusion, LBP possesses a variety of hepato-protective properties which make it a potent supplementary therapeutic agent against NASH in future clinical trials. PMID:24998389

  4. Acute intravenous toxicity of dimethyl sulfoxide, polyethylene glycol 400, dimethylformamide, absolute ethanol, and benzyl alcohol in inbred mouse strains.

    PubMed

    Montaguti, P; Melloni, E; Cavalletti, E

    1994-04-01

    Acute intravenous toxicity of some solvents, i.e. dimethyl sulfoxide (DMSO), polyethylene glycol 400 (PEG 400), dimethylformamide (DMF), absolute ethanol (EtOH) and benzyl alcohol (BeOH), was determined in three inbred (CD2F1, B6D2F1 and C57BL/6N) mouse strains used in many preclinical tests, mainly in oncology and toxicology. Haemolytic and precipitation potential tests in vitro were performed to assess the blood compatibility of the investigated solvents and its relationship with the observed symptoms. The single tested solvents did not show any major differences in acute toxicity in the three tested strains with the exclusion of DMSO (less toxic in CD2F1) and BeOH and EtOH (less toxic in B6D2F1). The tested dose ranges in the three strains (in ml/kg) were 1.0-5.66 for DMSO, 2.0-8.0 for PEG 400, 1.0-4.0 for DMF, 0.75-4.24 for EtOH, 0.025-0.4 for BeOH. The lowest tested dose was a safe dose and the highest one was the dose causing mortality in no more than half the animals in each group. The in vitro results suggest avoiding the use of BeOH (which also is more toxic than the other solvents in the in vivo test) and DMSO and using PEG400, EtOH and DMF even though the latter induced a body weight decrease in the B6D2F1 mouse strain. As a general conclusion, dilution of these solvents in water is suggested to ameliorate their blood compatibility and the use of doses not higher than the lowest dose tested in this study is recommended. PMID:8011014

  5. Smoking, alcohol consumption, physical activity, and family history and the risks of acute myocardial infarction and unstable angina pectoris: a prospective cohort study

    Microsoft Academic Search

    Audrey HH Merry; Jolanda MA Boer; Leo J Schouten; Edith JM Feskens; WM Monique Verschuren; Anton PM Gorgels; Piet A van den Brandt

    2011-01-01

    Background  Few studies investigated the association between smoking, alcohol consumption, or physical activity and the risk of unstable\\u000a angina pectoris (UAP), while the strength of these associations may differ compared to other coronary diseases such as acute\\u000a myocardial infarction (AMI). Therefore, we investigated whether the associations of these lifestyle factors with UAP differed\\u000a from those with AMI. Additionally, we investigated whether

  6. LPSF/GQ-02 Inhibits the Development of Hepatic Steatosis and Inflammation in a Mouse Model of Non-Alcoholic Fatty Liver Disease (NAFLD)

    PubMed Central

    Soares e Silva, Amanda Karolina; de Oliveira Cipriano Torres, Dilênia; dos Santos Gomes, Fabiana Oliveira; dos Santos Silva, Bruna; Lima Ribeiro, Edlene; Costa Oliveira, Amanda; dos Santos, Laise Aline Martins; de Lima, Maria do Carmo Alves; Pitta, Ivan da Rocha; Peixoto, Christina Alves

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extends from simple steatosis to non-alcoholic steatohepatitis. Although the pathogenesis of NAFLD remains undefined, it is recognized that insulin resistance is present in almost all patients who develop this disease. Thiazolidinediones (TZDs) act as an insulin sensitizer and have been used in the treatment of patients with type 2 diabetes and other insulin-resistant conditions, including NAFLD. Hence, therapy of NAFLD with insulin-sensitizing drugs should ideally improve the key hepatic histological changes, while also reducing cardiometabolic and cancer risks. Controversially, TZDs are associated with the development of cardiovascular events and liver problems. Therefore, there is a need for the development of new therapeutic strategies to improve liver function in patients with chronic liver diseases. The aim of the present study was to assess the therapeutic effects of LPSF/GQ-02 on the liver of LDLR-/- mice after a high-fat diet. Eighty male mice were divided into 4 groups and two different experiments: 1-received a standard diet; 2-fed with a high-fat diet (HFD); 3–HFD+pioglitazone; 4–HFD+LPSF/GQ-02. The experiments were conducted for 10 or 12 weeks and in the last two or four weeks respectively, the drugs were administered daily by gavage. The results obtained with an NAFLD murine model indicated that LPSF/GQ-02 was effective in improving the hepatic architecture, decreasing fat accumulation, reducing the amount of collagen, decreasing inflammation by reducing IL-6, iNOS, COX-2 and F4 / 80, and increasing the protein expression of I?B?, cytoplasmic NF?B-65, eNOS and IRS-1 in mice LDLR -/-. These results suggest a direct action by LPSF/GQ-02 on the factors that affect inflammation, insulin resistance and fat accumulation in the liver of these animals. Further studies are being conducted in our laboratory to investigate the possible mechanism of action of LPSF/GQ-02 on hepatic lipid metabolism. PMID:25875942

  7. Acute Alcohol Consumption and Secondary Psychopathic Traits Increase Ratings of the Attractiveness and Health of Ethnic Ingroup Faces but Not Outgroup Faces

    PubMed Central

    Mitchell, Ian J.; Gillespie, Steven M.; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

    2015-01-01

    Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition.

  8. Alcoholism and Alcohol Abuse

    MedlinePLUS

    ... causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that ... more alcohol to feel the same effect With alcohol abuse, you are not physically dependent, but you still ...

  9. Protective effects of HFE7A, mouse anti-human/mouse Fas monoclonal antibody against acute and lethal hepatic injury induced by Jo2

    PubMed Central

    Watanabe, Kenji; Takahashi, Shu; Ichikawa, Kimihisa

    2009-01-01

    HFE7A is a mouse anti-human/mouse Fas monoclonal antibody which, protects mice from fulminant hepatitis induced by Jo2. Herein, we report on the mechanism of the protective effect of HFE7A against Jo2-induced acute and lethal hepatic injury. HFE7A reduced the serum aminotransferase level which was elevated after Jo2 injection. HFE7A also inhibited caspase activation and mitochondrial depolarization in hepatocytes derived from apoptosis induced by Jo2 injection. The protective effect of HFE7A against Jo2-induced apoptosis in mouse hepatocytes was reproducible in vitro. The cell death and caspase activation in isolated mouse hepatocytes were induced by incubating these cells with Jo2 in vitro, and HFE7A inhibited the cell death and caspase activation in mouse hepatocytes in a dose-dependent manner. The affinity of HFE7A to mouse Fas was lower than that of Jo2. The binding of Jo2 to neither recombinant mouse Fas nor mouse hepatocytes was inhibited by an excessive amount of HFE7A. Interestingly, HFE7A bound to hepatocytes isolated from Fas knockout mice. From these results, it is suggested that HFE7A may exert a protective effect against Jo2-induced hepatitis not by competitively inhibiting the binding of Jo2 to Fas on hepatocytes, and that a distinct molecule other than Fas may possibly be involved in the protective effect of HFE7A against Jo2-induced hepatic injury. PMID:20024619

  10. Limited theraputic effect of n-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alcohol-related steatohepatitis is associated with increased oxidative stress, DNA damage, lipotoxicity, and insulin resistance in liver. Hypothesis: Since inflammation and oxidative stress can promote insulin resistance, effective treatment with anti-oxidants, e.g. N-acetylcysteine (NAC), may rest...

  11. Seven Novel Mutations in Bulgarian Patients with Acute Hepatic Porphyrias (AHP).

    PubMed

    Dragneva, Sonya; Szyszka-Niagolov, Monika; Ivanova, Aneta; Mateva, Lyudmila; Izumi, Rumiko; Aoki, Yoko; Matsubara, Yoichi

    2014-01-01

    Acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP) are caused by mutations in the hydroxymethylbilane synthase (HMBS), protoporphyrinogen oxidase (PPOX), and coproporphyrinogen oxidase (CPOX) genes, respectively. This study aimed to identify mutations in seven Bulgarian families with AIP, six with VP, and one with HCP. A total of 33 subjects, both symptomatic (n?=?21) and asymptomatic (n?=?12), were included in this study. The identification of mutations was performed by direct sequencing of all the coding exons of the corresponding enzymes in the probands. The available relatives were screened for the possible mutations. A total of six different mutations in HMBS were detected in all seven families with AIP, three of which were previously described: c.76C>T [p.R26C] in exon 3, c.287C>T [p.S96F] in exon 7, and c.445C>T [p.R149X] in exon 9. The following three novel HMBS mutations were found: c.345-2A>C in intron 7-8, c.279-280insAT in exon 7, and c.887delC in exon 15. A total of three different novel mutations were identified in the PPOX gene in the VP families: c.441-442delCA in exon 5, c.917T>C [p.L306P] in exon 9, and c.1252T>C [p.C418R] in exon 12. A novel nonsense mutation, c.364G>T [p.E122X], in exon 1 of the CPOX gene was identified in the HCP family. This study, which identified mutations in Bulgarian families with AHP for the first time, established seven novel mutation sites. Seven latent carriers were also diagnosed and, therefore, were able to receive crucial counseling to prevent attacks. PMID:24997713

  12. Acute exposure to high-fat diets increases hepatic expression of genes related to cell repair and remodeling in female rats.

    PubMed

    Miller, Colette N; Morton, Heidi P; Cooney, Paula T; Winters, Tricia G; Ramseur, Keshia R; Rayalam, Srujana; Della-Fera, Mary Anne; Baile, Clifton A; Brown, Lynda M

    2014-01-01

    High-fat diets (HFD) promote the development of both obesity and fatty liver disease through the up-regulation of hepatic lipogenesis. Insulin resistance, a hallmark of both conditions, causes dysfunctional fuel partitioning and increases in lipogenesis. Recent work has demonstrated that systemic insulin resistance occurs in as little as the first 72 hours of an HFD, suggesting the potential for hepatic disruption with HFD at this time point. The current study sought to determine differences in expression of lipogenic genes between sexes in 3-month-old male and female Long-Evans rats after 72 hours of a 40% HFD or a 17% fat (chow) diet. Owing to the response of estrogen on hepatic signaling, we hypothesized that a sexual dimorphic response would occur in the expression of lipogenic enzymes, inflammatory cytokines, apoptotic, and cell repair and remodeling genes. Both sexes consumed more energy when fed an HFD compared with their low fat-fed controls. However, only the males fed the HFD had a significant increase in body fat. Regardless of sex, HFD caused down-regulation of lipogenic and inflammatory genes. Interestingly, females fed an HFD had up-regulated expression of apoptotic and cell repair-related genes compared with the males. This may suggest that females are more responsive to the acute hepatic injury effects caused by HFDs. In summary, neither male nor female rats displayed disrupted hepatic metabolic pathways after 72 hours of the HFD treatment. In addition, female rats appear to have protection from increases in fat deposition, possibly due to increased caloric expenditure; male rats fed an HFD were less active, as demonstrated by distance traveled in their home cage. PMID:24418250

  13. Hypertonic saline resuscitation enhances blood pressure recovery and decreases organ injury following hemorrhage in acute alcohol intoxicated rodents

    PubMed Central

    Sulzer, Jesse K.; Whitaker, Annie M.; Molina, Patricia E.

    2012-01-01

    Background Acute alcohol intoxication (AAI) impairs the hemodynamic and arginine vasopressin (AVP) counter-regulation to hemorrhagic shock (HS) and lactated Ringer’s (LR) fluid resuscitation (FR). The mechanism of AAI-induced suppression of AVP release in response to HS involves accentuated nitric oxide (NO) inhibitory tone. In contrast, AAI does not prevent AVP response to increased osmolarity produced by hypertonic saline (HTS) infusion. We hypothesized that FR with HTS during AAI would enhance AVP release by decreasing PVN NO inhibitory tone subsequently improving mean arterial blood pressure (MABP) and organ perfusion. Methods Male Sprague Dawley rats received a 15h alcohol infusion (2.5g/kg + 0.3 g/kg/h) or dextrose (DEX) prior to HS (40mmHg × 60 min) and FR with HTS (7.5%; 4ml/kg) or LR (2.4 × blood volume removed). Organ blood flow was determined and brains collected for NO content at 2h post-FR. Results HTS improved MABP recovery in AAI (109 vs 80mmHg) and DEX (114 vs 83mmHg) animals compared to LR. This was associated with higher (>60%) circulating AVP levels at 2h post-FR than those detected in LR animals in both groups. Neither AAI alone nor HS in DEX animals resuscitated with LR altered organ blood flow. In AAI animals, HS and FR with LR reduced blood flow to liver (72%), small intestine (65%), and large intestine (67%) compared to shams. FR with HTS improved liver (3-fold) and small intestine (2-fold) blood flow compared to LR in AAI-HS animals. The enhanced MABP response to HTS was prevented by pretreatment with a systemic AVP V1a receptor antagonist. HTS decreased PVN NO content in both groups 2h post-FR. Conclusions These results suggest that FR with HTS in AAI results in removal of central NO inhibition of AVP, restoring AVP levels and improving MABP and organ perfusion in AAI-HS. PMID:23147176

  14. Reduced Susceptibility of DNA Methyltransferase 1 Hypomorphic (Dnmt1N\\/+) Mice to Hepatic Steatosis upon Feeding Liquid Alcohol Diet

    Microsoft Academic Search

    Huban Kutay; Corie Klepper; Bo Wang; Shu-hao Hsu; Jharna Datta; Lianbo Yu; Xiaoli Zhang; Sarmila Majumder; Tasneem Motiwala; Nuzhat Khan; Martha Belury; Craig McClain; Samson Jacob; Kalpana Ghoshal

    2012-01-01

    BackgroundMethylation at C-5 (5-mdC) of CpG base pairs, the most abundant epigenetic modification of DNA, is catalyzed by 3 essential DNA methyltransferases (Dnmt1, Dnmt3a and Dnmt3b). Aberrations in DNA methylation and Dnmts are linked to different diseases including cancer. However, their role in alcoholic liver disease (ALD) has not been elucidated.Methodology\\/Principal FindingsDnmt1 wild type (Dnmt1+\\/+) and hypomorphic (Dnmt1N\\/+) male mice

  15. Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

    PubMed

    Lee, I-C; Baek, H-S; Kim, S-H; Moon, C; Park, S-H; Kim, S-H; Shin, I-S; Park, S-C; Kim, J-C

    2015-03-01

    This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-? (TNF-?) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-? and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities. PMID:24972622

  16. Spontaneous recovery in acute human hepatitis C virus infection: functional T-cell thresholds and relative importance of CD4 help.

    PubMed

    Smyk-Pearson, Susan; Tester, Ian A; Klarquist, Jared; Palmer, Brent E; Pawlotsky, Jean-Michel; Golden-Mason, Lucy; Rosen, Hugo R

    2008-02-01

    The mechanisms mediating protective immunity to hepatitis C virus (HCV) infection are incompletely understood because early infection in humans is rarely identified, particularly in those individuals who subsequently demonstrate spontaneous virus eradication. We have established a large national network of patients with acute HCV infection. Here, we comprehensively examined total HCV-specific CD4(+) and CD8(+) T-cell responses and identified functional T-cell thresholds that predict recovery. Interestingly, we found that the presence of HCV-specific cytotoxic T lymphocytes (CTLs) that can proliferate, exhibit cytotoxicity, and produce gamma interferon does not ensure recovery, but whether these CTLs were primed in the presence or absence of CD4(+) T-cell help (HCV-specific interleukin-2 production) is a critical determinant. These results have important implications for early prediction of the virologic outcome following acute HCV and for the development of novel immunotherapeutic approaches. PMID:18045940

  17. Reduction of endotoxin attenuates liver fibrosis through suppression of hepatic stellate cell activation and remission of intestinal permeability in a rat non-alcoholic steatohepatitis model

    PubMed Central

    DOUHARA, AKITOSHI; MORIYA, KEI; YOSHIJI, HITOSHI; NOGUCHI, RYUICHI; NAMISAKI, TADASHI; KITADE, MITSUTERU; KAJI, KOSUKE; AIHARA, YOSUKE; NISHIMURA, NORIHISA; TAKEDA, KOSUKE; OKURA, YASUSHI; KAWARATANI, HIDETO; FUKUI, HIROSHI

    2015-01-01

    Previous clinical studies have demonstrated that endotoxin/toll-like receptor 4 (TLR4) signaling is critical in the inflammatory pathways associated with non-alcoholic steatohepatitis (NASH). In human and animal studies, NASH was associated with portal lipopolysaccharide (LPS) and the plasma LPS level was hypothesized to be associated with small intestinal bacterial overgrowth, change in composition of the microbiota and increased intestinal permeability. The aim of the present study was to investigate the roles of endogenous endotoxin and TLR4 in the pathogenesis of NASH. The effects of antibiotics were assessed in vivo using a choline deficiency amino acid (CDAA)-induced experimental liver fibrosis model. Antibiotics, including polymyxins and neomycins, were orally administered in drinking water. Antibiotics attenuated hepatic stellate cell (HSC) activation and liver fibrosis via TGF-? and collagen in an experimental hepatic fibrosis model. The mechanism by which antibiotics attenuated LPS-TLR4 signaling and liver fibrosis was assessed. Notably, TLR4 mRNA level in the liver was elevated in the CDAA group and the CDAA-induced increase was significantly reduced by antibiotics. However, no significant differences were observed in the intestine among all groups. Elevated mRNA levels of LPS binding protein, which was correlated with serum endotoxin levels, were recognized in the CDAA group and the CDAA-induced increase was significantly reduced by antibiotics. The intestinal permeability of the CDAA group was increased compared with the choline-supplemented amino acid group. The tight junction protein (TJP) in the intestine, determined by immunohistochemical analysis was inversely associated with intestinal permeability. Antibiotics improved the intestinal permeability and enhanced TJP expression. Inhibition of LPS-TLR4 signaling with antibiotics attenuated liver fibrosis development associated with NASH via the inhibition of HSC activation. These results indicated that reduction of LPS and restoration of intestinal TJP may be a novel therapeutic strategy for treatment of liver fibrosis development in NASH. PMID:25421042

  18. CALL TO ACTION TO SCALE UP GLOBAL HEPATITIS RESPONSE

    E-print Network

    Straight, Aaron

    CALL TO ACTION TO SCALE UP GLOBAL HEPATITIS RESPONSE Background Viral hepatitis is now responsible hepatitis and some 2 billion have been infected with hepatitis B virus. Most people with chronic hepatitis B, contributing to global increases in both of these chronic diseases. Millions of acute infections with hepatitis

  19. Alcohol-Related Diarrhea

    Microsoft Academic Search

    Nischita K. Reddy; Ashwani Singal; Don W. Powell

    \\u000a Diarrhea related to alcohol abuse may be either acute or chronic. Acute diarrheas are the result of dietary indiscretion,\\u000a transient anatomic or motility changes of the stomach or small intestine, impaired nutrient absorption, mucosal barrier function\\u000a or pancreatic secretion as well as hormonal\\/cytokine abnormalities related to alcohol hangover. Chronic diarrheas may result\\u000a from alcohol withdrawal, pancreatic or hepatobiliary dysfunction, morphologic

  20. Severe drug induced acute hepatitis associated with use of St John’s wort (Hypericum perforatum) during treatment with pegylated interferon ?

    PubMed Central

    Piccolo, Paola; Gentile, Silvia; Alegiani, Filippo; Angelico, Mario

    2009-01-01

    A 61-year-old woman with chronic hepatitis C received peginterferon ? 180 ?g/week, and obtained undetectable qualitative hepatitis C virus (HCV) RNA (lower limit of detection 50 IU/ml) after 8 weeks of treatment. Shortly thereafter aminotransferase values greatly increased (>20 × upper limit of normal) and did not decline after treatment suspension. The patient admitted taking St John’s wort (Hypericum perforatum) for depressed mood, recommended by a friend, during the preceding 6 weeks. Liver function tests continued to worsen and international normalised ratio (INR) prolongation developed; the patient was hospitalised. Test for antinuclear antibody was positive (1:320) and treatment with methylprednisolone was started; bilirubin and aminotransferase levels slowly declined, though a new flare occurred when steroids were tapered. After 6 months of prednisone treatment, the liver function tests returned to baseline levels. The combination of peginterferon ? and St John’s wort resulted in a severe acute hepatitis in this patient. Patients should be advised of this potential toxic effect of this herbal remedy. PMID:21686643

  1. Hepatitis E virus: do locally acquired infections in Australia necessitate laboratory testing in acute hepatitis patients with no overseas travel history?

    PubMed Central

    Shrestha, Ashish C.; Faddy, Helen M.; Flower, Robert L. P.; Seed, Clive R.; Keller, Anthony J.

    2015-01-01

    Summary Hepatitis E virus (HEV) is emerging as a global public health threat. Water-borne HEV outbreaks are common in developing countries and are associated with genotypes 1 and 2. In industrialised countries, sporadic cases of zoonotic transmission associated with genotypes 3 and 4 are increasingly being reported. Transfusion- and transplantation-transmitted HEV have been documented, although ingestion of contaminated food is thought to be the major transmission route. Severe disease is possible and chronic hepatitis infection occurs in solid-organ-transplant recipients and in patients with immunosuppressive disorders. In Australia, HEV cases are mainly travellers returning from disease endemic countries. Indeed, there are few reported cases of locally acquired HEV. Pigs in Australia have been shown to be infected with HEV, which indicates the possibility of zoonotic transmission. The extent of locally acquired infection is not known, however it may be greater than expected and may necessitate laboratory testing in patients reporting no overseas travel. PMID:25560836

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

    PubMed Central

    Kim, Yu Ri; Ban, Jung Ok; Yoo, Hwan Soo; Lee, Yong Moon; Yoon, Yeo Pyo; Eum, So Young; Jeong, Heon Sang; Yoon, Do-young; Han, Sang Bae; Hong, Jin Tae

    2013-01-01

    High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500?mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50?mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1?, MIP-1?, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity. PMID:23935693

  3. Alcoholic liver disease: Treatment

    PubMed Central

    Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

    2014-01-01

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

  4. Trouble with Bleeding: Risk Factors for Acute Hepatitis C among HIV-Positive Gay Men from Germany—A Case-Control Study

    PubMed Central

    Schmidt, Axel J.; Rockstroh, Jürgen K.; Vogel, Martin; An der Heiden, Matthias; Baillot, Armin; Krznaric, Ivanka; Radun, Doris

    2011-01-01

    Objectives To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. Background Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. Methods Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. Results 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. Conclusions Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding. PMID:21408083

  5. Role of p38 Mapk in development of acute hepatic injury in Long-Evans Cinnamon (LEC) rats, an animal model of human Wilson's disease.

    PubMed

    Kadowaki, Shingo; Meguro, Saori; Imaizumi, Yoshitaka; Sakai, Hiroshi; Endoh, Daiji; Hayashi, Masanobu

    2013-12-30

    The Long-Evans Cinnamon (LEC) rat, an animal model of human Wilson's disease, spontaneously develops fulminant hepatitis associated with severe jaundice at about 4 months of age. In this study, we examined the changes in gene expression during progression of acute hepatic injury. When levels of gene expression in the liver of LEC rats at 13 weeks of age were compared to those in rats at 4 weeks of age using oligonucleotide arrays, 1,620 genes out of 7,700 genes analyzed showed more than 2-fold differences. Expression levels of 11 of 29 genes related to stress-activating protein kinase (SAPK) changed by more than 2-fold in the liver of LEC rats, but none of the SAPK-related genes showed changes in expression levels in the liver of control rats. Activity of p38 mapk in the liver of LEC rats at 13 weeks of age was about 8.1-fold higher than that in rats at 4 weeks of age. When LEC rats were administered SB203580, a p38 mapk-specific inhibitor, by s.c. injection twice a week from 10 to 13 weeks of age, activities of p38 mapk in the liver, activities of AST and ALT and concentrations of bilirubin in sera of rats administered SB203580 significantly decreased compared to those in rats not administered. These results showed that the increase in activities of p38 mapk was related to the occurrence of acute hepatic injury in LEC rats. PMID:23877843

  6. Role of p38 Mapk in Development of Acute Hepatic Injury in Long-Evans Cinnamon (LEC) Rats, an Animal Model of Human Wilson’s Disease

    PubMed Central

    KADOWAKI, Shingo; MEGURO, Saori; IMAIZUMI, Yoshitaka; SAKAI, Hiroshi; ENDOH, Daiji; HAYASHI, Masanobu

    2013-01-01

    ABSTRACT The Long-Evans Cinnamon (LEC) rat, an animal model of human Wilson’s disease, spontaneously develops fulminant hepatitis associated with severe jaundice at about 4 months of age. In this study, we examined the changes in gene expression during progression of acute hepatic injury. When levels of gene expression in the liver of LEC rats at 13 weeks of age were compared to those in rats at 4 weeks of age using oligonucleotide arrays, 1,620 genes out of 7,700 genes analyzed showed more than 2-fold differences. Expression levels of 11 of 29 genes related to stress-activating protein kinase (SAPK) changed by more than 2-fold in the liver of LEC rats, but none of the SAPK-related genes showed changes in expression levels in the liver of control rats. Activity of p38 mapk in the liver of LEC rats at 13 weeks of age was about 8.1-fold higher than that in rats at 4 weeks of age. When LEC rats were administered SB203580, a p38 mapk-specific inhibitor, by s.c. injection twice a week from 10 to 13 weeks of age, activities of p38 mapk in the liver, activities of AST and ALT and concentrations of bilirubin in sera of rats administered SB203580 significantly decreased compared to those in rats not administered. These results showed that the increase in activities of p38 mapk was related to the occurrence of acute hepatic injury in LEC rats. PMID:23877843

  7. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

    PubMed Central

    Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

    1984-01-01

    The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

  8. Serum Testosterone Levels and Androgen Receptor CAG Polymorphism Correlate with Hepatitis B Virus (HBV)-Related Acute Liver Failure in Male HBV Carriers

    PubMed Central

    Xu, Bao-Yan; Tan, Wen-Ting; Tan, Shun; Dan, Yun-Jie; Luo, Xiao-Li; Deng, Guo-Hong

    2013-01-01

    Background Augmentation of androgen/androgen receptor (AR) pathway may influence chronic hepatitis B (CHB) more likely in males. AR activity is modulated by a polymorphic CAG repeat sequence in AR exon 1. This study aimed to investigate the relationship between serum testosterone levels, CAG repeat numbers and hepatitis B virus (HBV)-related acute liver failure (ALF). Methods Three hundred and seventy eight male CHB patients with ALF and 441 asymptomatic HBV carriers (AsCs) were recruited. AR CAG repeats numbers were analyzed. The serum testosterone levels of AsCs, ALFs and patients with hepatitis B flare groups, and sequential serum samples, were assessed quantitatively. Results The median CAG repeat (M-CAG) frequency was significantly higher in ALF patients than AsCs (P<0.001). Patients with M-CAG alleles (P<0.001, OR 3.0, 95% CI 2.1–4.2) had the highest risk for ALF. Serum testosterone levels were significantly higher (P<0.001) at hepatitis flare point (8.2±3.0 ng/mL) than inactive phase (6.4±2.0 ng/mL). CHB (8.30±2.71 ng/mL, P?=?7.6×10?6) and ALF group (2.61±1.83 ng/mL, P?=?1.7×10?17) had significantly different levels of testosterone in comparison with AsCs group (6.56±2.36 ng/mL). The serum testosterone levels sharply decreased from hepatitis flare phase to liver failure phase, and tended to be normal at the recovery phase. Male AsCs with M-CAG alleles had significantly lower serum testosterone levels (P<0.05). Conclusions There was a serum testosterone fluctuation during hepatitis B flare and HBV-related ALF, and the median CAG repeats in AR gene exon 1 were associated with lower serum testosterone levels in asymptomatic HBV carriers and an increased susceptibility to HBV-related ALF. PMID:24391916

  9. Clinical presentation of hepatitis E.

    PubMed

    Aggarwal, Rakesh

    2011-10-01

    Hepatitis E is a form of acute hepatitis, which is caused by infection with hepatitis E virus. The infection is transmitted primarily through fecal-oral route and the disease is highly endemic in several developing countries with opportunities for contamination of drinking water. In these areas with high endemicity, it occurs as outbreaks and as sporadic cases of acute hepatitis. The illness often resembles that associated with other hepatotropic viruses and is usually self-limiting; in some cases, the disease progresses to acute liver failure. The infection is particularly severe in pregnant women. Patients with chronic liver disease and superimposed HEV infection can present with severe liver injury, the so-called acute-on-chronic liver failure. In recent years, occasional sporadic cases with locally acquired hepatitis E have been reported from several developed countries in Europe, United States, and Asia. In these areas, in addition to acute hepatitis similar to that seen in highly endemic areas, chronic hepatitis E has been reported among immunosuppressed persons, in particular solid organ transplant recipients. HEV-infected mothers can transmit the infection to foetus, leading to premature birth, increased fetal loss and hypoglycaemia, hypothermia, and anicteric or icteric acute hepatitis in the newborns. Occasional cases with atypical non-hepatic manifestations, such as acute pancreatitis, hematological abnormalities, autoimmune phenomena, and neurological syndromes have been reported from both hyperendemic and non-endemic regions. The pathogenesis of these manifestations remains unclear. PMID:21458513

  10. Effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration, ROS production and lipid peroxidation in broiler chickens.

    PubMed

    Yang, Lin; Tan, Gao-Yi; Fu, Yu-Qiang; Feng, Jin-Hai; Zhang, Min-Hong

    2010-03-01

    In order to investigate the effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration, production of reactive oxygen species (ROS) and lipid peroxidation in broiler chickens, 128 six-week-old broiler chickens were kept in a controlled-environment chamber. The broiler chickens were initially kept at 25 degrees C (relative humidity, RH, 70+/-5%) for 6d and subsequently exposed to 35 degrees C (RH, 70+/-5%) for 3h, then the heat stress was removed and the temperature returned to 25 degrees C (RH, 70+/-5%). Blood and liver samples were obtained before heat exposure and at 0 (at the end of the three-hour heating episode, this group is also abbreviated as the HT group), 1, 2, 4, 8, 12h after the stress was removed. The results showed that acute heat stress induced a significant production of ROS, function of the mitochondrial respiratory chain, antioxidative enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)] activity, and formation of malondialdehybe (MDA). Within the first 12h after removal of the heat stress, the acute modification of the above parameters induced by heat stress gradually approached to pre-heat levels. The results of the present study suggest that acute exposure to high temperatures may depress the activity of the mitochondrial respiratory chain. This leads to over-production of ROS, which ultimately results in lipid peroxidation and oxidative stress. When the high temperature was removed, the production of ROS, mitochondrial respiratory function and oxidative injury that were induced by acute heat exposure gradually approached the levels observed before heating, in a time-dependent manner. PMID:19883793

  11. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients

    PubMed Central

    Obed, Aiman; Stern, Steffen; Jarrad, Anwar; Lorf, Thomas

    2015-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed.

  12. Polyphenol-rich extract of Nelumbo nucifera leaves inhibits alcohol-induced steatohepatitis via reducing hepatic lipid accumulation and anti-inflammation in C57BL/6J mice.

    PubMed

    Tang, Chang-Chieh; Lin, Wea-Lung; Lee, Yi-Ju; Tang, Yu-Chi; Wang, Chau-Jong

    2014-04-01

    The present study was undertaken to evaluate the hepatoprotective effect mechanisms of Nelumbo nucifera leaves extract (NLE) in experimental alcoholic steatohepatitis animal models. We found that the NLE contained polyphenols (phenolic acids and flavonoids), and more than 70% of the main functional components in NLE could potentially provide benefits for alcoholic liver disease. The parameters of histopathology, immunohistochemistry, antioxidant defense, proinflammatory mediator and lipid synthesis-related proteins demonstrated the inhibitory effect of NLE on alcoholic steatohepatitis. Plasma and hepatic content analysis showed that NLE inhibited lipid accumulation by altering the levels of triglycerides (TG) and cholesterol (TC). Treatment with NLE increased the expression of the p-AMPK/AMPK ratio and PPAR-?. Furthermore, fatty acid oxidation and transport via carnitine palmitoyltransferase-1 (CPT1) and microsomal triglyceride transfer protein (MTP) were through the activation of the AMPK and PPAR-? signal. These results revealed that the polyphenol-rich component of NLE prevents alcoholic steatohepatitis by multiple pathways, including reduced lipid synthesis, enhanced fatty acid oxidation and transport responses, inhibited oxidative stress and facilitated anti-inflammation. Suggesting that NLE might be regarded as a beneficial food that has the potential to be developed as a natural agent for preventing alcoholic steatohepatitis. PMID:24513924

  13. Alcoholic and non-alcoholic steatohepatitis.

    PubMed

    Neuman, Manuela G; French, Samuel W; French, Barbara A; Seitz, Helmut K; Cohen, Lawrence B; Mueller, Sebastian; Osna, Natalia A; Kharbanda, Kusum K; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J; McKillop, Iain H; Kirpich, Irina A; McClain, Craig J; Bataller, Ramon; Nanau, Radu M; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomes, Paul G; Ganesan, Murali; Malnick, Steve

    2014-12-01

    This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism. PMID:25217800

  14. Therapy for alcoholic liver disease

    PubMed Central

    Jaurigue, Maryconi M; Cappell, Mitchell S

    2014-01-01

    Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ? 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation. PMID:24605013

  15. Portal Vein Embolization with Radiolabeled Polyvinyl Alcohol Particles in a Swine Model: Hepatic Distribution and Implications for Pancreatic Islet Cell Transplantation

    SciTech Connect

    Owen, Richard J., E-mail: drrichardowen@tbwifi.c [University of Alberta, Department of Radiology and Diagnostic Imaging, Faculty of Medicine, Walter Mackenzie Health Sciences Center (Canada); Mercer, John R. [University of Alberta, Department of Oncologic Imaging, Faculty of Medicine (Canada); Al-Saif, Faisal; Molinari, Michele [University of Alberta Hospital, Department of Surgery (Canada); Ashforth, Robert A. [University of Alberta, Department of Radiology and Diagnostic Imaging, Faculty of Medicine, Walter Mackenzie Health Sciences Center (Canada); Rajotte, Ray V. [University of Alberta, Surgical-Medical Research Institute (Canada); Conner-Spady, Barbara [University of Alberta, Department of Radiology and Diagnostic Imaging, Faculty of Medicine, Walter Mackenzie Health Sciences Center (Canada); Shapiro, A. M. James [University of Alberta, Clinical Islet Transplant Program (Canada)

    2009-05-15

    The distribution of radiolabeled polyvinyl alcohol microspheres (PVAMs) when infused into the portal vein of domestic swine was investigated, with the purpose of assessing implications for pancreatic islet cell transplantation. PVAMs measuring 100-300 {mu}m (Contour SE) and labeled with {sup 99m}Tc were infused into the main portal vein of 12 swine, with intermittent portal venous pressure measurements. The infusion catheter was introduced antegradely via direct or indirect cannulation of the portal vein. The liver was subsequently divided into anatomical segments. Radioactivity (decay corrected) was measured for {sup 99m}Tc microsphere synthesis, dose preparation, gross organ activities, tissue samples, and blood. Particulate labeling, catheter positioning, and infusion were successful in all cases. The number of particles used was (185,000 {+-} 24,000) with a volume of 1 ml. Mean portal pressure at 5 min was significantly higher than baseline, but without a significant difference at 15 min. Extrahepatic tissue and serum radioactivity was negligible. A significant difference in number of radioactive particles per gram was detected between segments 6/7 and segments 5/8. Intrasegmental activity was analyzed, and for segments 2/3 a significant difference in the percentage dose per gram across samples was demonstrated (P = 0.001). Effective and stable radiolabeling of PVAMs with {sup 99m}Tc-sulfur colloid was demonstrated. Portal venous infusion of 100- to 300-{mu}m particles showed entrapment in the sinusoidal hepatic system with transient portal pressure elevation. Preferential embolization into the right lateral and posterior segments occurs, suggesting that flow dynamics/catheter tip position plays a role in particle distribution.

  16. Frequent detection of antibodies to hepatitis B virus x-protein in acute, chronic and resolved infections

    Microsoft Academic Search

    J. Hess; M. Stemler; H. Will; C. H. Schröder; J. Kiihn; R. Braun

    1988-01-01

    Recombinant MS2-or ßgal fusion proteins containing parts of hepatitis B virus (HBV) HBx-, HBc-, and HBs-amino acid sequences were expressed in Escherichia coli and were used to screen 96 and 60 serum samples of HBV infected and uninfected patients, respectively, for the corresponding antibodies by immunoblotting. Antibodies against HBx were detected in 20 out of 65 sera of patients with

  17. Surveillance for Viral Hepatitis - United States, 2012

    MedlinePLUS

    ... Page Share Compartir Surveillance for Viral Hepatitis – United States, 2012 Entire report in a printable format [PDF - ... 1 Reported cases of acute hepatitis A, by state ? United States, 2008–2012 Table 2.2 Clinical ...

  18. Hepatic and pulmonary toxicogenomic profiles in mice intratracheally instilled with carbon black nanoparticles reveal pulmonary inflammation, acute phase response, and alterations in lipid homeostasis.

    PubMed

    Bourdon, Julie A; Halappanavar, Sabina; Saber, Anne T; Jacobsen, Nicklas R; Williams, Andrew; Wallin, Håkan; Vogel, Ulla; Yauk, Carole L

    2012-06-01

    Global pulmonary and hepatic messenger RNA profiles in adult female C57BL/6 mice intratracheally instilled with carbon black nanoparticles (NPs) (Printex 90) were analyzed to identify biological perturbations underlying systemic responses to NP exposure. Tissue gene expression changes were profiled 1, 3, and 28 days following exposure to 0.018, 0.054, and 0.162 mg Printex 90 alongside controls. Pulmonary response was marked by increased expression of inflammatory markers and acute phase response (APR) genes that persisted to day 28 at the highest exposure dose. Genes in the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase pathway were increased, and those involved in cholesterol efflux were decreased at least at the highest dose on days 1 and 3. Hepatic responses mainly consisted of the HMG-CoA reductase pathway on days 1 (high dose) and 28 (all doses). Protein analysis in tissues and plasma of 0.162 mg Printex 90-exposed mice relative to control revealed an increase in plasma serum amyloid A on days 1 and 28 (p < 0.05), decreases in plasma high-density lipoprotein on days 3 and 28, an increase in plasma low-density lipoprotein on day 28 (p < 0.05), and marginal increases in total hepatic cholesterol on day 28 (p = 0.06). The observed changes are linked to APR. Although further research is needed to establish links between observations and the onset and progression of systemic disorders, the present study demonstrates the ability of NPs to induce systemic effects. PMID:22461453

  19. Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 predicts prognosis of acute-on-chronic hepatitis B liver failure.

    PubMed

    Gao, S; Ji, X-F; Li, F; Sun, F-K; Zhao, J; Fan, Y-C; Wang, K

    2015-02-01

    The G-protein-coupled bile acid receptor Gpbar1 (TGR5) has been demonstrated to be able to negatively regulate hepatic inflammatory response. In this study, we aimed to determine the methylation status of TGR5 promoter in patients with acute-on-chronic hepatitis B liver failure (ACHBLF) and its predictive value for prognosis. We enrolled 76 consecutive ACHBLF patients, 80 chronic hepatitis B (CHB) patients and 30 healthy controls (HCs). Methylation status of TGR5 promoter in peripheral mononuclear cell (PBMC) was detected by methylation-specific polymerase chain reaction (MSP). The mRNA level of TGR5 was determined by quantitative real-time polymerase chain reaction (RT-qPCR). We found that the frequency of TGR5 promoter methylation was significantly higher in ACHBLF (35/76, 46.05%) than CHB patients (5/80, 6.25%; ?(2) = 32.38, P < 0.01) and HCs (1/30, 3.33%; ?(2) = 17.50, P < 0.01). TGR5 mRNA level was significantly lower (Z = -9.12, P < 0.01) in participants with aberrant methylation than those without. TGR5 methylation showed a sensitivity of 46.05% (35/76), specificity of 93.75% (75/80), positive predictive value (PPV) of 87.5% (35/40) and negative predictive value (NPV) of 64.66% (75/116) in discriminating ACHBLF from CHB patients. ACHBLF patients with methylated TGR5 showed significantly poor survival than those without (P < 0.01). When used to predict 3-month mortality of ACHBLF, TGR5 methylation [area under the receiver operating characteristic curve (AUC) = 0.75] performed significantly better than model for end-stage liver diseases (MELD) score (AUC = 0.65; P < 0.05). Therefore, our study demonstrated that aberrant TGR5 promoter methylation occurred in ACHBLF and might be a potential prognostic marker for the disease. PMID:24995843

  20. Hepatic and Pulmonary Toxicogenomic Profiles in Mice Intratracheally Instilled With Carbon Black Nanoparticles Reveal Pulmonary Inflammation, Acute Phase Response, and Alterations in Lipid Homeostasis

    PubMed Central

    Bourdon, Julie A.; Halappanavar, Sabina; Saber, Anne T.; Jacobsen, Nicklas R.; Williams, Andrew; Wallin, Håkan; Vogel, Ulla; Yauk, Carole L.

    2012-01-01

    Global pulmonary and hepatic messenger RNA profiles in adult female C57BL/6 mice intratracheally instilled with carbon black nanoparticles (NPs) (Printex 90) were analyzed to identify biological perturbations underlying systemic responses to NP exposure. Tissue gene expression changes were profiled 1, 3, and 28 days following exposure to 0.018, 0.054, and 0.162 mg Printex 90 alongside controls. Pulmonary response was marked by increased expression of inflammatory markers and acute phase response (APR) genes that persisted to day 28 at the highest exposure dose. Genes in the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase pathway were increased, and those involved in cholesterol efflux were decreased at least at the highest dose on days 1 and 3. Hepatic responses mainly consisted of the HMG-CoA reductase pathway on days 1 (high dose) and 28 (all doses). Protein analysis in tissues and plasma of 0.162 mg Printex 90–exposed mice relative to control revealed an increase in plasma serum amyloid A on days 1 and 28 (p < 0.05), decreases in plasma high-density lipoprotein on days 3 and 28, an increase in plasma low-density lipoprotein on day 28 (p < 0.05), and marginal increases in total hepatic cholesterol on day 28 (p = 0.06). The observed changes are linked to APR. Although further research is needed to establish links between observations and the onset and progression of systemic disorders, the present study demonstrates the ability of NPs to induce systemic effects. PMID:22461453

  1. Alcohol and immunology: introduction to and summary of the 2003 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

    PubMed

    Kovacs, Elizabeth J; Jerrells, Thomas R

    2004-07-01

    The 8th Meeting of the Alcohol and Immunology Research Interest Group (AIRIG) was held at Loyola University Medical Center, Maywood, Illinois, USA, on November 21, 2003. Reports from multiple laboratories reveal that the functional integrity of the immune system is of paramount importance to the survival of the individual after infection or injury. Evidence supports the idea that exposure to alcohol causes dysregulation of both the innate and the adaptive arms of the immune system. Gaining a better understanding of how alcohol interferes with normal inflammatory and immunoregulatory processes will aid researchers in the design of therapeutic interventions that can be used to improve these responses to better fight infection and maintain the health of the individual. At this meeting, nine speakers presented a summary of their recent work on the combined effects of ethanol and injury, infection, or inflammatory challenge. Topics were (1) T-cell activation after chronic ethanol ingestion in mice, (2) effect of ethanol consumption on the severity of acute viral-mediated pancreatitis, (3) ethanol and alveolar macrophage dysfunction, (4) impaired intestinal immunity and barrier function: a cause for enhanced bacterial translocation in alcohol intoxication and burn injury, (5) immune consequences of the combined insult of acute ethanol exposure and burn injury, (6) consequences of alcohol-induced dysregulation of immediate hemodynamic and inflammatory responses to trauma/hemorrhage, (7) regulation of tumor necrosis factor-alpha production by Kupffer cells after chronic exposure to ethanol, (8) acute exposure to ethanol and suppression of cytokine responses induced through Toll-like receptors, and (9) inhibition of antigen-presenting cell functions by alcohol: implications for hepatitis C virus infection. We anticipate that the work presented at the 8th Meeting of AIRIG, summarized in this article, and presented in the nine articles to follow in this Special Issue of Alcohol will stimulate ideas that will develop into research projects in these topical areas. PMID:15596084

  2. Hepatitis C

    MedlinePLUS

    Hepatitis C is a viral disease that leads to swelling (inflammation) of the liver. Other types of viral hepatitis ... Hepatitis C infection is caused by the hepatitis C virus (HCV). You can catch hepatitis C if the blood ...

  3. Cell Culture and Animal Models of Viral Hepatitis. Part I: Hepatitis B

    Microsoft Academic Search

    Chandan Guha; Sankar Mohan; Namita Roy-Chowdhury; Jayanta Roy-Chowdhury

    2004-01-01

    According to estimates, the hepatitis B virus (HBV) infects ?2 billion people glob- ally, producing a spectrum of disease including acute and chronic viral hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HBV and hepatitis C virus (HCV) infections constitute the most common indication for liver transplantation in the United States and Europe. A vaccine is now available to prevent acute HBV

  4. Role of Hypoxia Inducing Factor-1? in Alcohol-Induced Autophagy, Steatosis and Liver Injury in Mice

    PubMed Central

    Ni, Hong-Min; Bhakta, Amar; Wang, Shaogui; Li, Zhenrui; Manley, Sharon; Huang, Heqing; Copple, Bryan; Ding, Wen-Xing

    2014-01-01

    Chronic alcohol causes liver hypoxia and steatosis, which eventually develops into alcoholic liver disease (ALD). While it has been known that alcohol consumption activates hepatic hypoxia inducing factor-1? (HIF-1?), conflicting results regarding the role of HIF-1? in alcohol-induced liver injury and steatosis in mice have been reported. In the present study, we aimed to use hepatocyte-specific HIF-1? knockout mice to eliminate the possible compensatory effects of the single knockout of the 1? subunit of HIF to study the role of HIFs in ALD. C57BL/6 wild type mice were treated with acute ethanol to mimic human binge drinking. Matched wild-type and hepatocyte specific HIF-1? knockout mice were also subjected to a recently established Gao-binge alcohol model to mimic chronic plus binge conditions, which is quite common in human alcoholics. We found that acute alcohol treatment increased BNIP3 and BNIP3L/NIX expression in primary cultured hepatocytes and in mouse livers, suggesting that HIF may be activated in these models. We further found that hepatocyte-specific HIF-1? knockout mice developed less steatosis and liver injury following the Gao-binge model or acute ethanol treatment compared with their matched wild type mice. Mechanistically, protection against Gao-binge treatment-induced steatosis and liver injury was likely associated with increased FoxO3a activation and subsequent induction of autophagy in hepatocyte-specific HIF-1? knockout mice. PMID:25536043

  5. Assessing Women’s Sexual Arousal in the Context of Sexual Assault History and Acute Alcohol Intoxication

    PubMed Central

    Gilmore, Amanda K.; Schacht, Rebecca L.; George, William H.; Otto, Jacqueline M.; Davis, Kelly Cue; Heiman, Julia R.; Norris, Jeanette; Kajumulo, Kelly F.

    2011-01-01

    Introduction Few studies have examined differences in women’s sexual arousal based on sexual assault history (SAH) or in-the-moment alcohol intoxication. Only one has examined combined effects. Findings regarding the relationship between SAH and arousal are contradictory. Aim We aimed to determine the relationship between SAH, alcohol intoxication, and sexual arousal. Main Outcome Measures Genital response was measured by vaginal pulse amplitude (VPA) using vaginal photoplethysmography while watching erotic films. Self-reported sexual arousal was assessed after watching erotic films. Methods Women were randomly assigned to an alcohol (target blood alcohol level = .10%) or control condition and categorized as having a SAH or not. After beverage administration, all women watched erotic films while genital arousal (vaginal pulse amplitude; VPA) was measured. Afterwards self-reported sexual arousal was measured. Results Women with a SAH had smaller increases in genital arousal in response to the films than women without a SAH. Intoxicated women had smaller increases in genital arousal than sober women. However, no differences for SAH or intoxication were found in self-reported arousal. Conclusion SAH and alcohol intoxication are associated with smaller increases in genital arousal compared to women without a SAH and sober women, suggesting that these co-occurring factors impact sexual arousal. PMID:20367775

  6. Pyogenic Liver Abscess Correlates With Increased Risk of Acute Pancreatitis: A Population-Based Cohort Study

    PubMed Central

    Lai, Shih-Wei; Liao, Kuan-Fu; Lin, Cheng-Li; Chen, Pei-Chun

    2015-01-01

    Background The aim of this study was to explore whether there is a relationship between pyogenic liver abscess (PLA) and subsequent risk of acute pancreatitis in Taiwan. Methods Using inpatients claims data from the Taiwan National Health Insurance Program, we identified 30 866 subjects aged 20–84 years with the first-attack of PLA from 2000 to 2010 as the PLA group and randomly selected 123 464 subjects without PLA as the non-PLA group. The incidence of the first attack of acute pancreatitis at the end of 2010 and the risk associated with PLA and other comorbidities were measured. Results The overall incidence of acute pancreatitis was 3.84-fold greater in the PLA group than in the non-PLA group (4.61 vs 1.19 events per 1000 person-years; 95% CI, 3.43–4.29). After controlling for potential confounding factors, the adjusted hazard ratio of acute pancreatitis was 3.00 (95% CI, 2.62–3.43) for the PLA group, as compared to the non-PLA group. Further analysis showed that compared to subjects with neither PLA nor comorbidities, patients with PLA and hypertriglyceridemia, biliary stones, alcoholism, or hepatitis C had greater risk of acute pancreatitis than those with PLA alone. Conclusions PLA correlates with increased risk of subsequent acute pancreatitis. Comorbidities, including hypertriglyceridemia, biliary stones, alcoholism, and hepatitis C, may enhance the risk of developing acute pancreatitis. PMID:25716281

  7. Toll-like receptor 4 plays an anti-HBV role in a murine model of acute hepatitis B virus expression

    PubMed Central

    Chang, Wen-Wei; Su, Ih-Jen; Lai, Ming-Derg; Chang, Wen-Tsan; Huang, Wenya; Lei, Huan-Yao

    2005-01-01

    AIM: Toll-like receptor 4 (TLR4) has been shown to be important for bacterial infection, especially to lipopolysaccharide signaling. Its possible role in HBV infection is studied in the present study. MATERIALS AND METHODS: pHBV3.6 plasmid, containing full-length HBV genome was used in the murine model of acute HBV expression by hydrodynamics in vivo transfection. TLR4 normal or mutant mouse strain was compared to investigate the possible role of TLR4 in acute HBV expression. RESULTS: After pHBV3.6 injection, the infiltrating leukocytes expressed TLR4 were observed nearby the HBsAg-expressing hepatocytes. The HBV antigenemia as well as the replication and transcription were higher in TLR4-mutant C3H/HeJ mice than in normal C3H/HeN mice. The HBV-specific immune responses were impaired in the liver or spleen of the C3H/HeJ mice. Their inducible nitric oxide synthase (iNOS) expression on the hepatic infiltrating cells was also impaired. When adoptively transferring splenocytes from C3H/HeN mice to C3H/HeJ mice, the HBV replication was inhibited to the level as that of C3H/HeN. CONCLUSION: These results suggest that TLR4 plays an anti-HBV role in vivo through the induction of iNOS expression and HBV-specific immune responses after HBV expression. PMID:16425356

  8. Alcohol-Induced miR-27a Regulates Differentiation and M2 Macrophage Polarization of Normal Human Monocytes.

    PubMed

    Saha, Banishree; Bruneau, Johanna C; Kodys, Karen; Szabo, Gyongyi

    2015-04-01

    Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection-mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16(+) and CD68(+) and M2-type (CD206(+), dendritic cell [DC]-SIGN(+)-expressing and IL-10-secreting) circulating CD14(+) monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Overexpression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization. PMID:25716995

  9. Treatment of Alcoholic Liver Disease

    PubMed Central

    Bergheim, Ina; McClain, Craig J.; Arteel, Gavin E.

    2009-01-01

    Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60% (worse than many common cancers such as breast and prostate). The cornerstone for therapy for ALD is lifestyle modification, including drinking cessation and treatment of decompensation, if appropriate. Nutrition intervention has been shown to play a positive role on both an in-patient and out-patient basis. Corticosteroids are effective in selected patients with alcoholic hepatitis, and treatment with pentoxifylline appears to be a promising anti-inflammatory therapy. Recent studies have indicated anti-TNF? therapy, at least for alcoholic hepatitis. Some complementary and alternative medicinal agents, such as milk thistle and S-adenosylmethionine, may be effective in alcoholic cirrhosis. Treatment of the complications of ALD can improve the quality of life and, in some cases, decrease short-term mortality. PMID:16508292

  10. Enhancement of the hypothalamic-pituitary-adrenal axis but not cytokine responses to stress challenges imposed during withdrawal from acute alcohol exposure in Sprague-Dawley rats

    PubMed Central

    Buck, Hollin M.; Hueston, Cara M.; Bishop, Christopher; Deak, Terrence

    2011-01-01

    Rationale Alcohol withdrawal is associated with reduced activity, increased anxiety, and other signs of distress. Objective The goal of the current studies was to determine whether acute ethanol exposure would alter hypothalamic-pituitary-adrenal (HPA) axis reactivity and cytokine responses to stress challenges imposed during the withdrawal period. Methods Male Sprague-Dawley rats were intubated with 4g/kg of ethanol to simulate acute binge-like ethanol intake. After characterizing the blood ethanol concentrations (BECs; Experiment 1), exploratory activity in a novel environment was explored at 10, 14 and 18 hr after ethanol (Experiment 2) to characterize altered activity patterns indicative of withdrawal. In Experiment 3, rats were exposed to footshock during withdrawal to examine whether prior ethanol exposure would alter cytokine and HPA axis responses to stress. Experiments 4–5 investigated HPA axis sensitivity and gene expression changes during restraint imposed during withdrawal. Results Prior ethanol exposure produced a period of stress hyper-reactivity evidenced by an enhanced HPA axis response (increased corticosterone and adrenocorticotropic hormone) observed during withdrawal. While this hyper-reactivity in response to two different stress challenges (novel environment and restraint) was accompanied by profound behavioral changes indicative of withdrawal, no alterations in cytokine changes evoked by stress were observed. Conclusions Taken together, these findings provide support for the hypothesis that alcohol withdrawal enhances HPA axis reactivity to stress challenges, though not likely not as the result of heightened inflammatory signaling, and may have implications for understanding the mechanisms by which stress impacts relapse drinking in humans. PMID:21735074

  11. Decreased Systemic Clearance of Diltiazem with Increased Hepatic Metabolism in Rats with Uranyl Nitrate-Induced Acute Renal Failure

    Microsoft Academic Search

    Yong-Hee Lee; Min-Hwa Lee; Chang-Koo Shim

    1992-01-01

    The effect of uranyl nitrate (UN)-induced acute renal failure (ARF) on the pharmacokinetics of diltiazem (DTZ) was examined in rats through in vitro and in vivo studies. In vitro homogenate studies demonstrated that DTZ was metabolized to deacetyl diltiazem (DAD) predominantly in the liver. Metabolism in the small intestine, kidney, or blood pool was negligible compared with that in the

  12. The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats

    Microsoft Academic Search

    Ammar C. Al-Rikabi

    2001-01-01

    The iron chelating activity of deferoxamine (DFO) has been exploited to obtain protection against the peroxidative damage in rat heart which was induced by the administration of an acute dose of doxorubicin (DXR, 25 mg kg?1, i.v.). The peroxidative lesions were evaluated both biochemically and histopathologically, 48 h after DXR administration. Abnormal biochemical changes including a marked increase in the

  13. Alcohol, host defence and society

    Microsoft Academic Search

    Steve Nelson; Jay K. Kolls

    2002-01-01

    Impaired health caused by alcohol abuse has been known throughout recorded history. Over the past century, alcohol abuse has been clearly linked to host susceptibility to infectious disease, particularly bacterial pneumonia. Recently, both acute and chronic alcohol intake have been shown to result in specific defects in innate and adaptive immunity; these could, in principle, be subjected to specific modulation

  14. Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis.

    PubMed

    Schwinge, Dorothee; Carambia, Antonella; Quaas, Alexander; Krech, Till; Wegscheid, Claudia; Tiegs, Gisa; Prinz, Immo; Lohse, Ansgar W; Herkel, Johannes; Schramm, Christoph

    2015-03-15

    Autoimmune liver diseases predominantly affect women. In this study, we aimed to elucidate how sex affects autoimmune hepatic inflammation. Acute experimental cholangitis was induced by adoptive transfer of OVA-specific CD8(+) T cells into mice, which express the cognate Ag on cholangiocytes. In contrast to previous mouse models of cholangitis, this model displayed a strong sexual dimorphism: female mice developed marked cholangitis, whereas male mice were resistant to cholangitis induction. The recruitment of endogenous CD4(+) T cells, but not transferred CD8(+) T cells into female livers was strongly increased. These cells expressed higher amounts of the proinflammatory cytokine IL-17, which was at least in part responsible for the liver inflammation observed. The recruitment of endogenous CD4(+) T cells was associated with increased expression of the chemokines CXCL-9 and CXCL-10 in female livers. The sex-specific factor responsible for the observed differences was found to be testosterone: male mice could be rendered susceptible to liver inflammation by castration, and testosterone treatment was sufficient to completely suppress liver inflammation in female mice. Accordingly, testosterone treatment of female mice significantly reduced the expression of IL-17A, CXCL-9, and CXCL-10 within the liver. Serum testosterone levels of untreated mice negatively correlated with the IL-17, CXCL-9, and CXCL-10 expression in the liver, further supporting a role for testosterone in hepatic immune homeostasis. In conclusion, testosterone was found to be the major determinant of the observed sexual dimorphism. Further study into the role of testosterone for liver inflammation could lead to novel treatment targets in human autoimmune liver diseases. PMID:25672751

  15. Moderate acute alcohol intoxication has minimal effect on surround suppression measured with a motion direction discrimination task.

    PubMed

    Read, Jenny C A; Georgiou, Renos; Brash, Claire; Yazdani, Partow; Whittaker, Roger; Trevelyan, Andrew J; Serrano-Pedraza, Ignacio

    2015-01-01

    A well-studied paradox of motion perception is that, in order to correctly judge direction in high-contrast stimuli, subjects need to observe motion for longer in large stimuli than in small stimuli. This effect is one of several perceptual effects known generally as "surround suppression." It is usually attributed to center-surround antagonism between neurons in visual cortex, believed to be mediated by GABA-ergic inhibition. Accordingly, several studies have reported that this index of surround suppression is reduced in groups known to have reduced GABA-ergic inhibition, including older people and people with schizophrenia and major depressive disorder. In this study, we examined the effect on this index of moderate amounts of ethanol alcohol. Among its many effects on the nervous system, alcohol potentiates GABA-ergic transmission. We therefore hypothesized that it should further impair the perception of motion in large stimuli, resulting in a stronger surround-suppression index. This prediction was not borne out. Alcohol consumption slightly worsened duration thresholds for both large and small stimuli, but their ratio did not change significantly. PMID:25583875

  16. Surgical Treatment of Non-Alcoholic Steatohepatitis and Non-Alcoholic Fatty Liver Disease

    Microsoft Academic Search

    R. A. Weiner

    2010-01-01

    Background: Overweight and obesity are the most significant risk factors for the development of hepatic steatosis, non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) in children and adults. Both have been increasingly implicated in the genesis of hepatic fibrosis and cirrhosis. However, no consensus exists about whether weight reduction may reverse this process. Methods: To assess the effect of

  17. Hepatitis C

    MedlinePLUS

    ... may include: Fatigue Nausea Vomiting Loss of appetite Jaundice (yellowing of the skin and the whites of ... vaccine for hepatitis C. (There are vaccines for hepatitis A and hepatitis B.) If you have hepatitis C, ...

  18. Therapeutic Hypothermia for Acute Liver Failure: Toward a Randomized, Controlled Trial in Patients with Advanced Hepatic Encephalopathy

    Microsoft Academic Search

    R. Todd Stravitz; William M. Lee; Andreas H. Kramer; David J. Kramer; Linda Hynan; Andres T. Blei

    2008-01-01

    Acute liver failure (ALF), the abrupt loss of liver function in a patient without previous liver disease, remains a highly\\u000a mortal condition. Patients with ALF of